Treatment of patients with a compressible attenuation device

ABSTRACT

Disclosed herein are methods of treating a patient, comprising providing a compressible attenuation device that is moveable from a first, introduction configuration to a second, implanted configuration. The attenuation device is introduced into a treatment site. In one embodiment, the treatment site is the bladder. In another embodiment, the treatment site is the abdominal cavity. The volume of the attenuation devices changes in response to pressure changes in the treatment site and attenuates pressure changes in the bladder.

This application is a continuation-in-part of U.S. patent applicationSer. No. 09/723,309 filed on Nov. 27, 2000 now U.S. Pat No. 6,682,473,which claims priority to U.S. Provisional Patent Application Ser. No.60/197,095, filed Apr. 14, 2000, and claims priority to U.S. ProvisionalPatent Application Ser. No. 60/415,949, filed Oct. 3, 2002; thedisclosures of the aforementioned applications are hereby incorporatedin their entirety herein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to methods and apparatus forattenuating and/or baffling transient pressure waves in relativelyincompressible materials in organs of the body, including, but notlimited to the following systems of the human body: cardiovascular,pulmonary, renal/urological, gastrointestinal, hepatic/biliary,gynecological, central nervous, musculoskeletal, otorhinolaryngical andophthalmic.

In one particular aspect, the present invention relates generally to thefield of urology and gynecology, and in particular to the treatment ofdisorders of the urinary tract caused by sudden fluctuations ofintravesical pressure. More specifically, in this aspect of the presentinvention, methods and devices are provided for the diagnosis andtreatment of urinary disorders such as incontinence, urgency, frequency,interstitial cystitis, irritable bladder syndrome and neurogenicbladders.

2. Description of the Related Art

Pressure waves are known to propagate through incompressible fluids invarious organs of the body. These pressure waves may be caused by anumber of events including events within the body, such as a beatingheart, breathing in the lungs, peristalsis actions in the GI tract,movement of the muscles of the body, or events such as coughing,laughing, external trauma to the body, and movement of the body relativeto gravity. As the elasticity of the surrounding tissues and organs,sometimes referred to as compliance, decreases, the propagation of thesepressure waves increases. These pressure waves have many undesirableeffects ranging from discomfort, to stress on the organs and tissue, tofluid leakage such as urinary incontinence, to renal failure, stroke,heart attack and blindness.

Pressure accumulators and wave diffusers are types of devices that canmodulate pressure waves in various nonanalogous settings. Accumulatortechnology is well known and used in hydraulic systems in aircraft,manufacturing equipment, and water supply and distribution since the1940s. Common types of accumulators include bladder accumulators, pistonaccumulators, non-separator (air over fluid), and weight loaded typeaccumulators.

Wave diffusers also affect the transmission of pressure waves inincompressible systems in various settings. The function of suchdiffusers is to interrupt the progress of a pressure wave and distributethe energy of the wave in so many directions so as to destroy theintegrity of a uniform wavefront and its resultant effects. Wavediffusers may be used to protect a specified area from the impact of awavefront.

Urinary tract disorders are a widespread problem in the United Statesand throughout the world, affecting people of all ages bothphysiologically and psychologically. Urinary tract disorders have anumber of causes including birth defects, disease, injury, aging, andurinary tract infection.

In light of the foregoing, a number of attempts have been made to combatthese disorders. One such attempt involves the use of an indwellingcatheter connected to a collection bag with a clamping device on thecatheter. Indwelling catheters, however, have a number of drawbacks. Forinstance, there is an infection risk associated with indwellingcatheters, which provide a direct passage for bacteria or othermicroorganisms into the bladder. Thus, indwelling catheters can only beused for relatively short-term situations. In addition, indwellingcatheters and associated collection bags are not cosmetically appealingto most patients.

An attempt at solving urinary incontinence involves the use ofprosthetic urethral valves. One such prior art valve utilizes aninflatable cuff that is inserted around the outside of the urethra. Theurethral valves of the prior art also have numerous disadvantages. Onedisadvantage of these valves is that they typically require surgery forinstallation, and some prior art valves must be operated externally andare therefore dependent on manual intervention.

The use of intra-urethral valves is also known. Typical intra-urethralvalves of the prior art also generally require manual intervention.Another problem associated with prior art intra-urethral valves is thatthe valves may be displaced into the bladder or expelled from theurethra. There is also an infection risk associated with many suchvalves since they often extend into the meatus and/or have portions ofthe device external to the urethra providing a passage formicroorganisms into the bladder.

Electrical stimulation therapy including rectal, intra-vaginal andexternal has been attempted to tone the muscles and stimulate nervessupporting the bladder and urethra. This therapy requires lengthy andnumerous treatments, and any benefits derived from the therapy typicallydiminish when the treatments are stopped.

Current surgical incontinence procedures typically focus on theaugmentation of urethral flow resistance. Prior art surgicalinterventions include bladder neck suspensions and bulk (collagen)injections. Although these procedures can be clinically effective withcertain patients, problems include widely variable clinical outcomes,relative high costs to perform, potential complications related tosurgery, and any effects may be short lived.

Drug therapy exists for a number of urinary tract conditions, includingoveractive bladder. These drugs include oral medications (systemic) anddrugs delivered directly into the bladder. These drugs typically sufferfrom side effects, lack of effectiveness and high morbidity. Oralmedications typically do not allow immediate relief of symptoms andincludes side effects such as dry mouth and constipation. Drugsdelivered directly into the bladder often require continuous orintermittent catheterization for introduction of the therapeutic agentsat the clinically appropriate time.

The intent of the treatment methods described to date either focus onthe augmentation of urethral flow resistance, the temporary stoppage orabsorption of all urethral flow, or relxing the detrusor muscles tominimize unwanted contractions. The disadvantages and limitations of theprior art treatments are numerous and include:

-   an excessively high level of patient interaction is typically    required to operate and/or maintain the devices, especially for    elderly patients and for physically or mentally challenged patients;-   limited clinical efficacy;-   restricted urine outflow;-   patient discomfort and side effects;-   urethral and bladder infections related to the devices used; and-   relatively expensive when compared to non-clinical solutions    (diapers, pads, etc.).

These prior art approaches do not address the reduction in dynamiccompliance which results in increased intravesical bladder pressure.

SUMMARY OF THE INVENTION

There is provided in accordance with one aspect of the presentinvention, a device for treating symptoms of a urinary tractdysfunction, comprising a compressible attenuation device having anexpanded volume within the range of from about 1 cc to about 400 cc, anda valve for permitting filling of the attenuation device through adelivery system.

In accordance with another aspect of the present invention, there isprovided a device for treating symptoms of a urinary tract dysfunction,comprising a compressible attenuation device having an expanded volumewithin the range of from about 1 cc to about 400 cc, and a valve havinga first membrane and a second membrane with a flow passage therebetweenfor filling the attenuation device.

In accordance with another aspect of the present invention, there isprovided a method of treating a patient after a radical prostatectomy,comprising the step of attenuating an increase in pressure within thebladder by reversibly reducing the volume of the attenuation device inresponse to the pressure.

Further features and advantages of the present invention will becomeapparent to those of skill in the art in view of the detaileddescription of preferred embodiments which follows, when consideredtogether with the attached drawings and claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates maximum urethral pressure against intravesicalpressure during normal voiding.

FIG. 2 illustrates the intravesical pressure exceeding the maximumurethral pressure in a noncompliant bladder.

FIG. 3 illustrates an intravesical pressure spike exceeding the maximumurethral pressure during stress incontinence.

FIG. 4A illustrates the relationship between intravesical pressure anddetrusor pressure during cough-induced urgency or frequency.

FIG. 4B illustrates the relationship between intravesical pressure anddetrusor pressure during non-cough-induced urgency or frequency.

FIG. 5 is a schematic top plan view of an inflatable attenuation devicein accordance with one aspect of the invention.

FIG. 5A is a side elevational cross-section through the attenuationdevice of FIG. 5.

FIG. 6 is a side elevational schematic view of a delivery system fordeploying an attenuation device in accordance with one aspect of thepresent invention.

FIG. 6A is a side elevational schematic view of one embodiment of thepresent invention.

FIG. 6B is a cross-section through the line 6B—6B in FIG. 6.

FIG. 7A is a fragmentary schematic view of the filling tube of adelivery system engaged within the valve of an attenuation device.

FIG. 7B is a fragmentary schematic view as in FIG. 7A, with the fillingtube proximally retracted from the valve.

FIGS. 8A–8E schematically illustrate different valve constructions foran inflatable attenuation device in accordance with the presentinvention.

FIG. 9 is a schematic representation of the delivery system of FIG. 6,transurethrally positioned within the bladder.

FIG. 10 is a schematic illustration as in FIG. 9, with the attenuationdevice inflated.

FIG. 11 is a schematic view of one embodiment of a delivery system inaccordance with the present invention, transurethrally positioned withinthe bladder.

FIG. 11A is a cross-section through one embodiment of the deliverysystem of FIG. 11.

FIG. 12 is a side elevational schematic view of an attenuation deviceremoval system in accordance with one aspect of the present invention.

FIG. 13 is a schematic view of a toroidal shaped attenuation deviceaccordance with one embodiment of the present invention.

FIG. 13A is a side elevational cross-section view through one embodimentof the attenuation device of FIG. 13.

FIG. 14 is a schematic view of a toroidal shaped attenuation device asin FIG. 13, with an integral baffle therein.

FIG. 14A is a side elevational cross-section view through one embodimentof the attenuation device of FIG. 14.

FIG. 15 is a schematic illustration of the attenuation device disruptingthe unitary progression of a pressure wavefront.

FIGS. 16A–D are schematic representations of a variety of inflatableattenuation devices in accordance with the present invention.

FIG. 17A is a side elevational schematic view of a bellows-typemechanically assisted attenuation device in an expanded configuration.

FIG. 17B is a side elevational schematic view of the attenuation deviceof FIG. 17A, in a compressed configuration attenuating a pressure spike.

FIG. 18 is a side elevational schematic view of a self-expanding grafttype mechanically assisted attenuation device.

FIG. 19A is a side elevational schematic view of a multiple chamberattenuation device in accordance with a further aspect of the presentinvention.

FIG. 19B is a schematic illustration of the multiple chamber attenuationdevice of FIG. 19A, in a deployed orientation to ensure retention withinthe bladder.

FIG. 20 is a side elevational schematic view of an inflatableballoon-type attenuation device, having a locatable balloon valvethereon.

FIG. 21 is a schematic perspective view of the attenuation device ofFIG. 20, aligned with the distal end of a delivery or removal system.

FIG. 22 is a fragmentary cross-sectional view through the distal end ofa delivery or removal system, and the proximal end of the valve on anattenuation device, illustrating the valve in a filling or drainingorientation.

FIG. 23 is a fragmentary cross-section as in FIG. 22, showing the valvein a sealed orientation.

FIG. 24 is a schematic cross-section through a bladder, showing anattenuation device therein, having an attached, external tether.

FIG. 25 is a schematic cross-section through a bladder, showing atwo-component attenuation device in which a primary compressiblecomponent is positioned within the bladder and a secondary inflatablecomponent is positioned within the urethra.

FIG. 25A is a cross-sectional schematic view as in FIG. 25, illustratingthe compression of the primary attenuation device in response toelevated abdominal pressure, and the corresponding expansion of thesecondary inflatable component.

FIG. 25B is an enlarged fragmentary schematic view of the inflatablecomponent in FIG. 25A.

FIG. 25C is a pressure curve showing the intravesical pressure comparedto the secondary balloon pressure.

FIG. 26 illustrates the effect on intravesical pressure of the presenceof an implanted attenuation device in accordance with the presentinvention.

FIG. 27 is a schematic cross-sectional view through a bladder, showingan attenuation device anchored to the bladder wall.

FIG. 28 is a schematic cross-sectional view showing a bladder, and thetransurethral placement of a dynamic compliancy measurement catheter inaccordance with the present invention.

FIG. 29 is a schematic cross-sectional view through a vessel,illustrating a tubular attenuation device therein.

FIG. 30A is a schematic cross-section of a left atrial appendage of theheart, having an attenuation device positioned therein.

FIG. 30B is a schematic cross-section as in 30A, showing a bellows-typeattenuation device positioned in the, left atrial appendage.

FIG. 31 is a schematic cross-section of a tubular attenuation devicepositioned within the colon.

FIG. 32A is a schematic top plan view of an inflatable attenuationdevice with a duckbill valve design.

FIG. 32B is a close-up view of the duckbill valve in FIG. 32A.

FIG. 33A is a schematic top plan view of an inflatable attenuationdevice with a ring valve design.

FIG. 33B is a schematic top plan view of an inflatable attenuationdevice with a fill/plug design.

FIG. 33C is a schematic top plan view of an inflatable attenuationdevice with a dome valve design.

FIG. 34A is an elevated side view of one embodiment of a delivery systemfor the attenuation device in accordance with one aspect of the presentinvention.

FIG. 34B is an elevated side view of one embodiment of a delivery systemfor the attenuation device with the attenuation device exposed andejected.

FIG. 35A is an elevated side view of one embodiment of a delivery systemfor the attenuation device in accordance with one aspect of the presentinvention.

FIG. 35B is an elevated side view of the inflatable attenuation devicein FIG. 35A with the sheath slid proximally and the attenuation deviceexposed.

FIG. 36 is a schematic top plan view of an inflatable attenuation devicewith a valve that prevents the influx and/or efflux of media to/from theattenuation device.

FIG. 37 is a cross-section through the line 288—288 in FIG. 36.

FIG. 38 is a schematic top plan view of a valve with two duckbillstructures that prevent the flow of media in both directions.

FIGS. 39A–D presents graphs of attenuation/pressure reduction vs. timefor various attenuation device air volumes.

FIGS. 40A and 40B illustrate the connective and elastic tissues in thesubmucosal layer of the bladder.

FIG. 41 shows a typical cystometrogram.

FIGS. 42 and 43 provide side elevational cross-sectional views of apartially collapsed bladder.

FIGS. 44A–D shows pressure vs. time curves generated by a bench topbladder simulator.

FIG. 45 is a schematic view of one embodiment of an accumulator.

FIG. 46 is a schematic view of a simple accumulator.

FIG. 47A is a schematic cross-sectional view through one embodiment ofan implantable self-inflating attenuation device.

FIG. 47B is a schematic cross-sectional view through one embodiment ofan implantable self-inflating attenuation device.

FIG. 47C is a schematic cross-sectional view through one embodiment ofan implantable self-inflating attenuation device.

FIG. 48A is side elevational schematic view of a delivery system fordeploying an implantable self-inflating attenuation device in accordancewith one aspect of the present invention.

FIG. 48B is a cross-section through the line 442—442 in FIG. 48A.

FIG. 48C is a schematic cross-sectional view through one embodiment ofan implantable self-inflating attenuation device.

FIG. 48D is an elevated schematic view of a delivery system fordeploying an implantable self-inflating attenuation device in accordancewith one aspect of the present invention.

FIG. 49 is a schematic representation of an attenuation device with highvapor pressure gases and/or fluids in accordance with one aspect of thepresent invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Embodiments of the present invention are directed to methods andapparatus for measuring and/or attenuating and/or baffling transientpressure waves in relatively incompressible materials in organs of thebody. Illustrative embodiments of the present invention discussed belowrelate generally to the fields of urology and gynecology, and inparticular to the treatment of disorders of the urinary tractexacerbated by sudden fluctuations in intravesical pressure. However, aswill be readily understood by those skilled in the art, and as describedbelow, the present invention is not limited to the fields of urology andgynecology and methods and apparatus of embodiments of the presentinvention may be used in other organs of the body as well to attenuateand/or baffle pressure transients or reversibly occupy intraorgan space.

Certain embodiments of the present invention dampen transientintravesical pressure including pressure spikes experienced by theurinary tract. During a high frequency transient pressure event, thebladder becomes a relatively non-compliant environment due to a numberof factors including the pelvic skeletal structure, the compressiveloads of contracting tissues bounding the bladder or the decreasedcompliance of the musculature, nerve or connective tissue of thebladder. The factors contributing to the reduced compliance of thebladder are aging, anatomic abnormalities or trauma to the structures ofthe pelvis and abdomen.

Urine is primarily composed of water and is virtually incompressible inthe typical pressure ranges present within the human bladder. Therelationship between the maximum urethral pressure and the intravesicalpressure for normal voiding of the bladder is well defined. Withreference to FIG. 1, relaxation of the urethra occurs before thedetrusor muscle contracts to cause the intravesical pressure 320 toexceed the urethral pressure 322 during normal voiding.

The bladder serves two mechanical functions: 1) low-pressure storage and2) high-pressure voiding. During the storage or filling phase, thebladder receives an influx of urine from the kidneys. Compliance of thebladder is defined as the ratio of the change in volume to the change inpressure, and the static compliance of the bladder is measured during atypical urodynamic evaluation. The static compliance index is measuredby filling the bladder to cystometric capacity and allowing thepressures to equilibrate for a time period of approximately sixtyseconds. The static compliance index is calculated by dividing thebladder capacity by the Detrusor pressure at the end of filling. Anormal bladder will typically exhibit static compliance between 15 and30 ml/cm H₂O. A low static compliance bladder typically will have acompliance index of less than 10 ml/cm H₂O. With reference to FIG. 2which illustrates different pressures for a non-compliant bladder, a lowstatic compliance bladder typically is poorly distensible and has a highend-filling pressure. The intravesical pressure 320 must increase tohigher levels to exceed the maximum urethral pressure 324. The steadystate compliance of the bladder is used to diagnose patients withnaturopathic problems such as damage to the lower motor neurons, uppermotor neurons, or multiple sclerosis. In addition, the steady statecompliance of the bladder is also used, in some cases, to attempt todiagnose problem of incontinence, including urgency, frequency andcystitis.

In general, intravesical pressure spikes result from volumetric tissuedisplacement in response to gravity, muscular activity or rapidacceleration. The lack of compliance of the bladder and the urinecontained in the bladder with respect to events of high frequency,result in minimal fluidic pressure attenuation of the higher frequencypressure wave(s) and results in high intravesical pressures that aredirectly transmitted to the bladder neck and urethra, which may or maynot cause detrusor contractions. Under these conditions, the urethra mayact as a volumetric pressure relief mechanism allowing a proportionalvolume of fluid to escape the bladder, to lower the intravesicalpressure to a tolerable level. The urethra has a maximum urethralpressure value, and when the intravesical pressure exceeds the maximumurethral pressure, fluid will escape the bladder. Under theseconditions, nerve receptors in the bladder and/or bladder neck and/ortrigone trigger a detrusor contraction that may lead to matriculation(frequency) or may subside without matriculation (urgency) or may leadto the intravesical pressure exceeding the maximum urethral pressureresulting in fluid escaping the bladder (incontinence). Under theseconditions, waves hitting and/or expanding the bladder wall, may cause apatient with cystitis to exhibit significant pain.

Incontinence is common in males who have undergone radicalprostatectomy, particularly where the sphincter has been compromised. Inthese patients, attenuation in the bladder reduces the intravesical peakpressures, resulting in less urine leakage. The attenuation requirementsin these patients can include short duration pressure changes—such as,for example, 50 to 400 ms—and long duration pressure changes—such as,for example, greater than 500 ms—depending on the magnitude of damage tothe urinary sphincter.

The inventors of the present application have recognized that for thevast majority of patients suffering from problems of urinary tractdisorders such as frequency, urgency, stress and urge incontinence andcystitis, the cause and/or contributor to the bladder dysfunction is areduction of overall dynamic bladder compliance rather than steady statebladder compliance. These patients may often have bladders that arecompliant in steady state conditions, but have become non dynamicallycompliant when subjected to external pressure events having a shortduration of, for example, less than 5 seconds or in some cases less than2 seconds or even less than 0.5 seconds. Reduction in dynamic complianceof the bladder is often caused by some of the same conditions asreduction of steady state compliance including aging, use, distention,childbirth and trauma. The anatomical structure of the bladder inrelation to the diaphragm, stomach, and uterus (for women) causesexternal pressure to be exerted on the bladder during talking, walking,laughing, sitting, moving, turning, and rolling over.

The relationship between intravesical pressure 320 and the maximumurethral pressure 324 for a patient suffering from stress incontinencedue to lack of dynamic compliance in the bladder is illustrated in FIG.3. When the patient coughs (or some other stress event occurs), if thebladder does not have sufficient dynamic compliance in that frequencyrange a spike 326 will occur in the intravesical pressure. Intravesicalpressure spikes in excess of 120 cm H₂O have been urodynamicallyrecorded during coughing, jumping, laughing or sneezing. When theintravesical pressure exceeds the maximum urethral pressure value,leakage occurs. In order to retain urine during an intravesical pressurespike, the urinary retention resistance of the continent individual mustexceed the pressure spike. Urinary retention resistance can besimplified as the sum total of the outflow resistance contributions ofthe urethra, bladder neck and meatus. In female patients, it isgenerally believed that the largest resistance component is provided bythe urethra. One measure of urinary resistance is the urodynamicmeasurement of urethral leak pressure. The incontinent individualtypically has a urethral leak pressure less than 80 cm H₂O. The declineof adequate urinary retention resistance has been attributed to a numberof factors including reduced blood flow in the pelvic area, decreasedtissue elasticity, neurological disorders, deterioration of urethralmuscle tone and tissue trauma.

In practice, the urethral leak point pressure is determined by fillingthe bladder with a known amount of fluid and measuring the intravesicaland abdominal pressures when there is a visible leak from the urethrawhile the patient is “bearing-down” (valsalva). With an attenuationdevice in the bladder, the measured intravesical leak point pressuretypically increases due to the adsorption of some the abdominal energyby the attenuation device. In this case, the patient has to push harderto achieve the same intravesical pressure. Since the abdominal musclesand muscles surrounding the urethra both contract simultaneously duringa valsalva maneuver, the measured intravesical leak point pressure andurethral resistance increases when the attenuation device is in thebladder.

Urinary disorders, such as urgency, frequency, otherwise known asoveractive bladder, and interstitial cystitis are caused or exacerbatedwhen rapid pressure increases or rapid volume increases or otherirritable conditions within the bladder cause motor neurons to sendsignals to the brain to begin the cascade of events necessary forurination. External pressure exerted on the bladder may result in adetrusor contraction that may result in urgency, frequency orincontinence. See FIGS. 4A (cough-induced urgency/frequency) and 4B(non-cough-induced urgency/frequency). With reference to FIG. 4A, acoughing event 328 induces increased intravesical pressure 320 whichresults in increased detrusor pressure 330. An increase in the detrusorpressure 330 generally is associated with increased urgency, frequency,or incontinence. Urinary disorders such as interstitial cystitis orirritable bladder conditions are a chronic inflammatory condition of thebladder wall, which includes symptoms of urgency and/or frequency inaddition to pain. Therefore, the problem of a pressure spike in thefunctionally noncompliant bladder can be further exacerbated by a nearlysimultaneous contraction of the bladder and a relaxation of the urethra.

Certain embodiments of the present invention provide for methods anddevices for measuring and reporting the dynamic compliance of thebladder. One method of determining dynamic compliance includes the rapidinfusion of a volume of fluid into the bladder with immediatemeasurement of the intravesical pressure. The volume would be more than50 ccs, preferably greater than 100 cc and more preferably greater than200 cc. The rate of infusion would be less than 10 seconds, preferablyless than 5 seconds, and more preferably less than 2 seconds. Oneembodiment of the present invention includes a two lumen catheter placedwithin the bladder, wherein a compliant balloon is rapidly filled with anon-compliant material, such as saline is infused through one lumen ofthe catheter. The resulting intravesical pressure is measured from theother lumen of the catheter. This infusion can be with a syringe, amechanically assisted syringe or pump.

An additional embodiment provides methods and devices for treatingand/or compensating for reduced dynamic compliance of the bladder. Inone embodiment, a device having a compressible element is placed withinthe human urinary bladder, in a manner that allows the compressibleelement to act as a pressure accumulator or attenuator to attenuatetransient pressure events. The term accumulator refers generally todevices that attenuate pressure, force, or energy in a given locale byabsorbing and/or shifting away said pressure, force, or energy from saidlocale. The term attenuator refers generally to devices that attenuatepressure, force, or energy by dissipating or dampening said pressure,force, or energy. Gases such as atmospheric air, carbon dioxide andnitrogen are very compressible in the pressure ranges typicallyencountered in the human bladder, and these gases may be used inattenuation devices inserted in the bladder. Furthermore, when comparedto the tissues encompassing urine, these gases are significantly morecompliant than the immediate environment. The addition of aproportionately smaller volume of unpressurized gas acts as a low ratespring in series with the native fluidic circuit of the urinary tract.Additional information on the basic scientific principles underlyingpressure accumulators and methods for controlling transient changes inpressure can be found in E. BENJAMIN WYLIE ET AL., FLUID TRANSIENTS INSYSTEMS §§ 6, 10, 11, 13 (1993); the entirety of these sections arehereby incorporated by reference herein and made a part of thisspecification.

Accumulators can be designed to keep the pressure from exceeding apredetermined value or to prevent low pressures. Accumulators can bedesigned to protect against rapid transients as well as againstlonger-period surges in a system. One example of an accumulator is aclosed container partially filled with the system liquid and topped withair or gas. The gas may be in contact with the liquid, in which case anair compressor, or gas supply, is used to maintain the proper mass ofair or gas, or the gas may be separated from the liquid by a flexiblemembrane or a piston. The accumulator generally operates at the localsystem pressure. With reference to the embodiment illustrated in FIG.45, if the valve 302 of the accumulator 300 is closed abruptly the flow304 enters the air chamber 306, the air is compressed, and the flow tothe main pipeline 308 is gradually reduced as the pressure builds up,thereby provides a way to reduce the peak pressure in the chamber 306,the main pipeline 308, and other downstream plumbing and equipment.

In one embodiment, shown in FIG. 46, a single accumulator 300 is assumedto have the same pressure throughout its volume at any given instant.Here, the compressibility of the liquid 310 in the vessel 312 isconsidered negligible compared with air compressibility. Assuminginertia and friction are negligible, the gas 314 is assumed to followthe reversible polytropic relation H_(A)V^(n)=C_(A), where H_(A) is theabsolute head equal to the gage plus barometric pressure heads, whereV^(n) is the gas volume 316, where n is the polytropic exponent, andwhere C_(A) is a constant. The exponent n depends on the thermodynamicprocess followed by the gas 314 in the vessel 312. If a perfect gas isassumed, at one extreme the process may be isothermal, n=1, or at theother limit it may be isentropic, in which case n=1.4 for air. It shouldbe noted that computation of the aforementioned values, as well asanalogous or related values, can be determined by those skilled in theart by taking into consideration the foregoing discussion.

In another embodiment, the compression of the enclosed volume of aircreates heat that is dissipated into the relatively infinite heat sinkof the body. The balance of the energy absorbed by the compressed air issimply returned at a different, lower frequency into the fluidic circuitwhen the gas is allowed to expand, as the surrounding tissues return totheir initial positions. The addition of adequate local compliance caneffectively attenuate transient intravesical pressure spikes to levelsbelow the patient's leak pressure, thus obviating the need for relief bymeans of volumetric displacement of urine, and/or preventing thestimulation of signals to the brain that cause bladder contractions.

In accordance with one aspect of the present invention, an attenuationdevice is placed within the human urinary bladder. The attenuationdevice is intended to be untethered in the bladder and is intended toremain in the bladder for between several hours and one year, betweenone week and six months, or between one and three months. Theattenuation device is a small elastomeric air cell with a relaxed(unstretched) volume of between 1 and 500 cc, more preferably between 1and 100 cc and more preferably still, between 3 and 25 cc. Theattenuation device is a unitary component but can be comprised of two ormore subcomponents. The attenuation device has a substantially uniformwall thickness of between 0.25 inch to 0.0001 inch, more preferablybetween 0.0005 inch and 0.005 inch, but could be designed to varygreatly, and still perform the intended function. In the embodimentdescribed above, attenuation devices having air cells that arefree-floating in the bladder have been described. In other embodimentsof the present invention, air cells or similar attenuation devices couldbe surgically affixed to the bladder wall through the use of suture,staples and other accepted methods or placed submucosally orintramuscularly within the bladder wall. Other embodiments could alsoinclude attenuation devices with programmable, variable and adjustablebuoyancy by using ballasting, specific inflation/deflation solutions,alternative materials of construction or by other means.

Referring to FIGS. 5 and 5A, there is illustrated one embodiment of anattenuation device 66 which comprises a moveable wall such as on aninflatable container 68. The inflatable container 68 is illustrated ashaving a generally circular profile, although other profiles may beutilized in accordance with the present invention. The diameter of theinflatable container 68 may be varied within the range of from about0.25 inches to about 6 inches, in an application of the inventioninvolving the implantation of only a single attenuation device. Manyembodiments of the inflatable containers 68 will have a diameter withinthe range from about 1 inch to about 3 inches, with a total volumewithin the ranges recited above. In general, the specific dimensions andconfiguration of the inflatable container 68 are selected to produce anattenuation device having a desired volume and a desired dynamiccompression range, and may be varied from spherical to relatively flatas will be apparent to those of skill in the art based upon thedisclosure herein. In certain embodiments, two or three or more discreetinflatable containers 68 are utilized. The sum of the volumes of themultiple containers will equal the desired uncompressed displacement.

The inflatable container 68 illustrated in FIGS. 5 and 5A comprises aflexible wall 70, for separating the compressible contents of theattenuation device 66 from the external environment. Flexible wall 70comprises a first component 74 and second component 76 bonded togethersuch as by a seam 78. In the illustrated embodiment, the first component74 and second component 76 are essentially identical, such that the seam78 is formed on the outer periphery of the inflatable container 68. Seam78 may be accomplished in any of a variety of manners known in themedical device bonding arts, such as heat bonding, adhesive bonding,solvent bonding, RF or laser welding, or others known in the art.

The flexible wall 70 formed by a bonded first component 74 and secondcomponent 76 define an interior cavity 72. As is discussed elsewhereherein, interior cavity 72 preferably comprises a compressible media,such as gas, or foam. Other media or structures capable of reduction involume through a mechanism other than strict compression may also beused. For example, a material capable of undergoing a phase change froma first, higher volume phase to a second, lower volume phase under thetemperature and pressure ranges experienced in the bladder may also beused.

In order to minimize trauma during delivery of the attenuation device66, the attenuation device is preferably expandable from a first,reduced cross-sectional configuration to a second, enlargedcross-sectional configuration. The attenuation device 66 may thus betransurethrally deployed into the bladder in its first configuration,and enlarged to its second configuration once positioned within thebladder to accomplish the pressure attenuation function. Preferably, acrossing profile or a greatest cross-sectional configuration of theattenuation device 66 when in the first configuration is no greater thanabout 24 French (8 mm), and, preferably, no greater than about 18 French(6 mm). This may be accomplished, for example, by rolling a deflatedinflatable container 68 about a longitudinal axis, while the interiorcavity 72 is evacuated.

Once positioned within the bladder, the interior cavity 72 is filledwith the compressible media to produce a functional attenuation device66. The present inventors contemplate fill pressures and volumes ofgenerally less than about 1.5 atmospheres and 50 ml, respectively, and,in some embodiments, less than 0.5 atmospheres and 25 ml, respectively,such as, for example, in the case of an air filled collapsibleattenuation device 66. In general, the fill pressure and volume arepreferably no more than necessary to keep the attenuation device 66inflated in the absence of pressure spikes. Excessive pressure andvolume within the attenuation device 66 may shorten the dynamic range ofthe attenuation device 66, thereby lessening the sensitivity toattenuate pressure spikes. Pressures of less than 1 atmosphere, or evenvacuums may be utilized if the structure of the attenuation device issufficient to balance the negative pressure to produce a net force suchthat attenuation can occur. This may be accomplished, for example, in anembodiment where the attenuation device 66 is provided with aself-expandable support structure (e.g. nitinol wire frame), whichprovides a radially outwardly directed bias.

The resiliency of the material of the attenuation device, and thepressure and volume of the inflation media are preferably matched toproduce a compression cycle time which is fast enough to allow theattenuation device to respond to increases in pressure while not have aclinically detrimental effect on voiding. For example, the attenuationdevice's compression cycle preferably bottoms out or reaches a maximumin a sufficiently short period of time as detrussor pressure increasesthat adverse clinical effects on voiding are minimized or prevented.

To facilitate filling the interior cavity 72 following placement of theattenuation device 66 within the bladder, the inflatable container 68 ispreferably provided with a valve 80. In the illustrated embodiment,valve 80 is positioned across the seam 78, and may be held in place bythe same bonding techniques utilized to form the seam 78. Valve 80 maybe omitted in an embodiment in which the attenuation device 66 isself-expandable.

Valve 80 generally comprises an aperture 82, for receiving a fillingtube therethrough. Aperture 82 is in fluid communication with theinterior cavity 72 by way of a flow path 83. At least one closure member84 is provided for permitting one way flow through flow path 83. In thismanner, a delivery system and filling device can be utilized to displaceclosure member 84 and introduce compressible media into the interiorcavity 72. Upon removal of the filling device, the closure member 84prevents or inhibits the escape of compressible media from the interiorcavity 72 through the flow path 83.

Thus, the closure member 84 is preferably movable between a firstorientation in which it obstructs effluent flow through the flow path 83and a second position in which it permits influent flow through the flowpath 83. Preferably, the closure member 84 is biased in the firstdirection. Thus, forward flow may be accomplished by either mechanicallymoving the closure member 84 into the second position such as using afilling tube, or by moving the closure member 84 into the secondposition by exerting a sufficient pressure on the compressible media inflow path 83 to overcome the closure bias. Certain specific valvestructures will be described in connection with FIGS. 8A–E below.However, any of a wide variety of valve designs may be utilized in theattenuation device 66 of the present invention as will be apparent tothose of skill in the art in view of the disclosure herein.

In one embodiment, the attenuation device consists of an air cellconsisting of 0.0018 inch thick polyurethane sheets that have beenbonded together to form a 2⅜ inch circle in top view. In one embodiment,the attenuation device is made from polyurethane and is intended to beinflated to a pressure slightly above atmospheric pressure and a volumeless than 50 ml or generally within the range of 0.01 to 1 psi aboveatmospheric pressure and less than 25 ml. Integral to the sealing edge78 of the attenuation device holds a port/valve 80 utilized in theplacement, inflation and release of the attenuation device. Into theport/valve structure 80 is placed the distal end of a rigid fill tube(0.050″ OD) 50. The valve 80 employed may be one of the valves describedin U.S. Pat. No. 5,144,708, which is incorporated herein by reference.In another embodiment, the attenuation device may be ultrasonically,radio frequency, adhesively or heat sealed in situ following inflation,in which case the valve may be omitted.

Biocompatible lubricating substances may be used to facilitate theplacement of the attenuation device/fill tube within the lumen of theintroducer. The distal tip of the introducer has been modified to allowa minimally traumatic presentation of the attenuation device to theurethral tissue. Biocompatible lubricating substances may be used tofacilitate the insertion of the attenuation device into the urethra.

In one embodiment, the attenuation device incorporates biocompatiblecoatings or fillers to minimize irritation to the bladder wall andmucosa and/or to inhibit the formation of mineral deposits(encrustation). The materials can be coated onto the surface orincorporated within the wall of the attenuation device.

Referring to FIG. 6, there is illustrated one delivery system fordeploying the attenuation device into the treatment site, such as, forexample, the bladder, in accordance with the present invention. Ingeneral, the delivery system 40 is designed to advance an attenuationdevice 66 (not illustrated) transurethrally into the bladder while in afirst, reduced cross-sectional configuration, and to thereafter inflateor enlarge or permit the expansion of the attenuation device to asecond, implanted orientation. The particular configuration andfunctionality of the delivery system 40 will therefore be governed inlarge part by the particular design of the attenuation device 66. Thus,as will be apparent to those of skill in the art in view of thedisclosure herein, various modifications and adaptations may becomedesirable to the particular delivery system disclosed herein, dependingupon the construction of the corresponding attenuation device.

The delivery system 40 comprises an elongate tubular body 42 having aproximal end 44 and a distal end 46. Tubular body 42 is dimensioned totransurethrally access the bladder. Thus, the tubular body 42 preferablyhas an outside diameter of no more than about 8 mm, and, preferably, nomore than about 4 mm. The length of the tubular body 42 may be varied,depending upon the desired proximal extension of the delivery system 42from the urethra during deployment. In general, an axial length oftubular body 42 within the range of from about 1″ to about 10″ for adultfemale patients and from about 4″ to about 30″ for adult male patientsis currently contemplated.

The tubular body 42 is provided with at least one central lumen 48extending axially therethrough. Central lumen 48 axially slideablyreceives a filling tube 50, for filling the attenuation device 66.Filling tube 50 comprises a tubular body 52 having a proximal end 54 anda distal end 58. An inflation lumen 60 extends throughout the length ofthe tubular body 52, and is in fluid communication with a proximal hub56. Hub 56 comprises a connector such as a standard luer connector forcoupling to a source of inflation media.

The tubular body 52 has an axial length which is sufficiently longerthan the axial length of tubular body 42 to allow the proximal hub 56 toremain accessible to the clinician and accomplish the functions ofdeploying and filling the attenuation device 66. In one embodiment, anouter tubular sheath (not illustrated) is slideably carried over thetubular body 42, and is spaced radially apart from the tubular body 52to define an annular cavity for receiving a rolled attenuation device 66therein. In this manner, the deflated attenuation device can be rolledaround a distal portion of the tubular body 52 and carried within thetubular sheath during transurethral placement. Once the delivery system40 has been properly positioned, proximal retraction of the outer sheathwith respect to the tubular body 52 exposes the deflated attenuationdevice 66. A source of inflation media is coupled to the proximal hub56, and media is introduced distally through central lumen 60 to inflatethe attenuation device 66. Following inflation of the attenuation device66, the delivery system 40 is disengaged from the attenuation device 66,such as by retracting the filling tube 50 with respect to the tubularbody 42. A distal stop surface 47 on tubular body 42 prevents proximalmovement of the attenuation device 66 as the filling tube 50 isproximally retracted. Delivery system 40 is thereafter removed from thepatient, leaving the inflated attenuation device 66 within the bladder.

With reference to FIGS. 6A and 6B, there is illustrated a modifiedversion of the delivery system 40. In this embodiment, a control 62 isconnected by way of a proximal extension 60 to the tubular body 52. Thecontrol 62 may be in any of a variety of forms, such as a knob or apistol grip. The control 62 may be grasped by the clinician, andutilized to axially advance or retract the filling tube 50 within thetubular body 42. The proximal hub 56 is connected to the tubular body 52by way of a bifurcation 61. As will be appreciated by those of skill inthe art, the central lumen 60 extends through the bifurcation 61 and tothe proximal hub 56. Proximal extension 60 may comprise a blockedtubular element or a solid element. An inflation source 64 such as asyringe filled with a predetermined volume of air or other media may beconnected to the proximal hub 56.

For patient comfort, the introducer is suitably sized to easily passthrough the urethra (approximately 0.5 to 4 mm diameter). Visualfeedback is provided to the clinician by means of insertion depthindicators along the longitudinal length of the introducer. Theintroducer may also have an adjustable depth stop that allows theclinician to pre-set the desired insertion depth. Once the deliverysystem has been inserted into the urethra to the desired depth theintroducer is then kept in a fixed position and the attenuation devicemounted on the distal end of the fill tube is then extended in the lumenof the bladder. The attenuation device is then filled with the indicatedvolume of gas from the attached syringe or similar device. See FIGS. 9,10, 11, and 11A. Once properly inflated, the attenuation device isreleased from the fill tube using the tip of the introducer as anopposing force disengaging the attenuation device valve from the filltube. The fill tube is then retracted completely into the lumen of theintroducer and the entire delivery system is then withdrawn from thepatient. The attenuation device is left in place for the clinicallyindicated period of time.

One aspect of the present invention relates to the delivery of a veryflexible, thin walled device. Delivery of an attenuation device istypically accomplished via a suitably sized introducer or possiblythrough the working channel of an endoscope or cystoscope. However, incertain instances the columnar strength of an attenuation device maymake it difficult to be pushed through such channels. A furtherrequirement of any delivery system is that it be atraumatic, and notpose a threat of tissue damage. This invention addresses such issues,and offers improvements for accomplishing delivery of such attenuationdevices as disclosed in co-pending applications U.S. application Ser.No. 60/197,095, filed Apr. 14, 2000, titled DEVICES AND METHODS FORBLADDER PRESSURE ATTENUATION, and U.S. application Ser. No. 09/723,309,filed Nov. 27, 2000, titled DEVICES AND METHODS FOR ATTENUATION OFPRESSURE WAVES IN THE BODY.

The attenuation device is normally folded on itself along its diameterin order to present a low profile for insertion into, for example, apatients bladder transurethrally. In this configuration the attenuationdevice has insufficient column strength to withstand the forces ofinsertion without buckling. If the attenuation device buckles it cannotbe inserted. Following insertion the attenuation device is inflated viaan inflation tube to which it is pre-mounted. After inflating theinflation tube is detached and the attenuation device is freed. By wayof illustration, various embodiments of the invention will be describedin the exemplary context of transurethral insertion of a delivery systeminto a patient's bladder.

In one embodiment, shown in FIGS. 34A and 34B, there is provided andelivery system for the attenuation device which consists of an innerfenestrated tubular member which is provided with an atraumatic roundedtip at its distal end, and an slideably mounted outer coaxial tubularmember. The rounded tip is shaped such that its proximal end, which isinserted into position in the distal end of the inner tubular member,presents essentially a “ramp” designed to aid ejection of theattenuation device from the fenestration when it is advanced. Theattenuation device to be delivered is attached to its inflation tube,folded as previously described, and drawn into the inner sheath throughthe fenestration. Once situated within the fenestration the outercoaxial tubular member is slid forward to close the fenestration, thuscontaining the bladder within the inner tube.

With reference to the embodiment illustrated in FIG. 34A, deliverysystem 370 comprises an inner sheath 372, a slideable outer sheath 374,an opening 376 in the inner sheath, and an atraumatic tip 378. Withreference to the embodiment illustrated in FIG. 34B, delivery system 370comprises an outer sheath 374 that slides backwards and an attenuationdevice 380. Here, the attenuation device 380 is exposed through theopening 376. The delivery system 370 comprises an inflation tube 382that is advanced toward the atraumatic tip 378, thereby causing theattenuation device 380 to be ejected. A curved ramp 384 in the deliverysystem 370 aids the ejection of the attenuation device 380.

In use the distal end of the delivery system is inserted through theurethra to an appropriate depth, the outer coaxial tube is slidbackwards along the inner tube, thus exposing the fenestration in theinner tube. The attenuation device is advanced using the inflation tubeand releases easily from the inner tube. The attenuation device isinflated, released from the inflation tube, and floats freely in thebladder.

In another embodiment, shown in FIGS. 35A and 35B, the attenuationdevice containment tube 386 is a simple open-ended cylinder. Theattenuation device 380 is folded as described previously and withdrawninto the containment tube 386. The open end of the containment tube 386would present a potentially traumatic edge to the urethra. In order toprevent such trauma, the open end of the containment tube 386 in thisinstance has rounded atraumatic end 378. This end 378 contains slits 388which, on sliding the containment tube 386 backwards allows the end 378to open, thus allowing deployment of the attenuation device 380 from thecontainment tube 386. On advancing the inflation tube 382 with theattenuation device 380 attached, the slits 388 open and present littlebarrier to the deployment of the attenuation device.

In another embodiment, the attenuation device is deliveredpercutaneously through the pelvis into the bladder. Similar topercutaneous access of arteries or veins, a needle is inserted throughthe skin and into the bladder. A guide wire is placed through the needleand the needle is removed leaving the guide wire in place. The deliverysystem and attenuation device are pushed into the bladder over the guidewire. The attenuation device is deployed and the delivery system andguide wire are removed. Guidance using ultrasound can also be employedto help guide the delivery system into the bladder.

In one embodiment, a removable delivery system is used to deliver,deploy, and fill the attenuation device. The delivery system can takethe form of the system taught by U.S. Pat. No. 5,479,945, titled methodand a removable device which can be used for the self-administeredtreatment of urinary tract infections or other disorders, issued Jan. 2,1996, the disclosure of which is incorporated in its entirety herein byreference.

With reference to FIGS. 7A and 7B, there is illustrated onedisengagement sequence for deploying the inflatable attenuation device66 from the delivery system 40 in accordance with one aspect of thepresent invention. As illustrated in FIG. 7A, the delivery system 40 isinitially configured with the filling tube 50 positioned within thevalve 80. The distal end 46 of outer tubular body 42 is dimensioned suchthat it will not fit through the aperture 82 of valve 80. Once theattenuation device 66 has been positioned within the bladder, theattenuation device 66 is inflated through filling tube 50.

With reference to FIG. 7B, the filling tube 50 is proximally retractedfollowing inflation so that it disengages from the valve 80. This isaccomplished by obstructing proximal movement of the attenuation device66 by stop surface 47 on the distal end 46 of tubular body 42. Theattenuation device 66 is thereafter fully disengaged from the deliverysystem 40, and the delivery system 40 may be removed.

With reference to FIGS. 8A, 32A, and 32B, there is illustrated aduckbill embodiment of the valve 80. Valve 80 comprises a tubular wall81, having an aperture 82 in communication with a flow path 83. At leastone closure member 84 is attached to the tubular wall, and extendsacross the flow path 83. In the illustrated embodiment, closure member84 comprises a first and a second duck bill valve leaflets 86 and 88which are attached at lateral edges 90 and 92 to the tubular wall. Theleaflets 86 and 88 incline medially in the distal direction to a pair ofcoaptive edges 94 and 96. This configuration allows forward flow throughflow path 83 to separate coaptive edges 94 and 96, thereby enablinginflation of the attenuation device 66. Upon removal of the inflationmedia source, the inflation media within the attenuation device 66 incombination with natural bias of the leaflets 86 and 88 cause theleaflets to coapt, thereby preventing effluent flow of inflation mediathrough the flow path 83.

The tubular body 81 and first and second leaflets 86 and 88 may bemanufactured from any of a variety of materials which will be apparentto those of skill in the art. For example, tubular body 81 may be madefrom polyurethane such as by extrusion. Leaflets 86 and 88 may be madefrom any of a variety of flexible materials such as polyurethane,silicone, or polyethylene, and may be bonded to the tubular element 81using adhesives, heat bonding, or other bonding techniques known in theart. Suitable valves include the valve manufactured by TargetTherapeutics and sold as the DSB silicon balloon to fill aneurysms andarterial-venous malformations.

With continued reference to FIGS. 8A, 32A, and 32B, in one method ofmanufacturing the attenuation device 66, the bushing 249 is RF welded tothe inflatable container 68 prior to installing the valve 80. Here, theduckbill valve 80 is bonded to the bushing 249 after welding. In onemethod of manufacturing the attenuation device 66, the mandrel isinstalled during welding, resulting in a polished surface with anair-tight seal along the inside of the tube.

Referring to FIG. 8B, closure is accomplished by two coaptive edges ondistal end 106 of tubular body 81. This construction is sometimesreferred to as a flapper valve. The tubular body 81 in this embodimentis formed by a first wall 96 and a second wall 100 which are bonded orfolded along a first edge 102 and a second edge 104 to define a flowpath 83 extending therethrough. The free distal ends of first and secondwalls 96 and 100 at the distal end 106 form coaptive leaflets, which maybe opened under forward flow pressure through the flow path 83 and willinhibit or prevent reverse flow through the flow path 83.

Referring to FIG. 8C, the proximal end of the flow path 83 on theflapper valve of FIG. 8B or other valve structure may be reinforced suchas by a reinforcing tube 108. Reinforcing tube 108 may be manufacturedin any of a variety of ways. For example, reinforcing tube 108 may beextruded from various densities of polyethylene, Pebax, polyurethane, orother materials known in the art. Reinforcing tube 108 may be desired tomaintain patency of the pathway to the valve 80, particularly in anembodiment adapted for coupling to a deflation and removal system aswill be discussed. In another embodiment, the reinforcing tube 108 maybe removable and used to prevent sealing of the valve during themanufacturing process and may also ease the placement of a fill tube inthe valve. This reinforcing tube 108 is removed after the manufacturingprocess is complete, or may be removed before, during, or after the filltube is placed.

With reference to FIGS. 8D and 33A, there is illustrated an additionalfeature that may additionally be incorporated into any of the valvesdiscussed above. In one embodiment of the this feature, an annularsealing ring 110 is provided on the interior surface of the tubular body81. Annular sealing ring 110 is adapted to provide a seal with thefilling tube 50, to optimize the filling performance of the attenuationdevice. Sealing ring 110 is thus preferably formed from a resilientmaterial such as silicone or polyurethane and dimensioned to slideablyreceive the filling tube 50 therethrough. In another embodiment, sealingwith the fill tube may be enhanced by restricting the aperture diameterwithout the use of a distinct sealing ring 110. Exemplary dimensions ofthe attenuation device 66 are shown in FIG. 33A.

With reference to FIGS. 8E and 33C, the valve may also be placed in thebody of the attenuation device, rather than in the seam. In oneexemplary embodiment, the through hole 258 has a diameter of 0.062inches. Here, the inflation channel 256 has a diameter of approximately0.063 to 0.070 inches. The valve can be placed in any number of waysincluding the methods described in U.S. Pat. No. 5,248,275, titledBalloon with flat film valve and method of manufacture, issued Sep. 28,1993, and U.S. Pat. No. 5,830,780, titled Self-closing valve structure,issued Nov. 3, 1998; both of these patents are hereby incorporated byreference herein and made a part of this specification.

In one embodiment, shown in FIG. 33B, the valve 80 has a fill/plug 250.In one method of manufacturing the fill/plug attenuation device 66, themandrel is installed during welding, resulting in a polished surfacewith an air-tight seal along the inside of the tube.

The attenuation device 66 is preferably also removable from the bladder.Removal may be accomplished in any of a variety of ways, depending uponthe construction of the attenuation device. Preferably, removal isaccomplished transurethrally. In one embodiment, removal is accomplishedby reducing the attenuation device 66 from its second enlarged profileto its first, reduced profile so that it may be withdrawntransurethrally by a removal system. The removal system will beconfigured differently depending upon whether reduction from the secondprofile to the first profile is accomplished by deflation, or bycompression. One embodiment of a removal system utilized to remove aninflatable attenuation device 66 will be described below in connectionwith FIG. 12.

In another embodiment, the removal procedure involves dissolving ordegrading the material or a portion of the material of the attenuationdevice 66 in situ. Material selection and wall thickness of theattenuation device 66 may be optimized to provide the desired usefullife of the attenuation device 66, followed by dissolution in theaqueous environment of the bladder. In one embodiment, dissolution ordeflation may be catalyzed or accelerated by an accelerating event suchas a change in pH or introduction of an initiator or accelerator intothe bladder, or reduction of pressure.

Attenuation devices having a predetermined dwell time after which theyare automatically voided advantageously eliminate the need for a removalprocedure. Such temporary attenuation devices can be manufactured in avariety of ways in accordance with the present invention, such asthrough the use of bioabsorbable or permeable materials. In oneembodiment, the entire wall of the inflatable container 68 is made froman absorbable material. As used herein “absorbable” means any materialwhich will dissolve, degrade, absorb or otherwise dissipate, regardlessof the chemical mechanism, to achieve the purpose recited herein. Inanother embodiment, only a portion of the flexible wall 70 or otherportion of the attenuation device such as the valve is made from anabsorbable material. As soon as one or more windows or “fuse” componentsof the attenuation device is absorbed, the attenuation device willdeflate through the resulting opening and can be expelled during normalvoiding. In yet another embodiment, one or more seams such as seam 78can be bonded by a dissolvable or absorbable material that is designedto fail after a predetermined time in the aqueous environment of thebladder.

The resulting deflated components from any of the foregoing time limitedembodiments can thereafter either be expelled during normal voiding, orcan remain in the bladder in a deflated state until removed using aremoval system. In one embodiment, the material or portion of theinflatable container 68 is made from a gas permeable material. As thegas dissipates from the inflatable container, its ability tospontaneously void increases. In one embodiment, the attenuation deviceis filled with approximately 20 ml of gas and the attenuation device'smaterial allows approximately 15 ml of gas to permeate out of theattenuation device over certain time intervals, such as, for example,one, three, six, or twelve months. Once the volume remaining is lessthan approximately 5 ml, the attenuation device is normally voided.

The predetermined dwell time within the bladder can be influenced by avariety of design factors, including the formulation of the absorbablematerial and the physical shape, thickness and surface area of theabsorbable component. A variety of absorbable polymers which can be usedin the present invention are known in the absorbable suture arts. Forexample, absorbable multifilament sutures such as DEXON sutures (madefrom glycolide homopolymer and commercially available from Davis & Geck,Danbury, Conn.), VICRYL sutures (made from a copolymer of glycolide andlactide and commercially available from Ethicon, Inc., Sommerville,N.J., and POLYSORB sutures (also made from a copolymer of glycolide andlactide and commercially available from United States SurgicalCorporation, Norwalk, Conn.) exemplify materials known in the industryand characterized as short term absorbable sutures. The classificationshort term absorbable sutures generally refers to surgical sutures whichretain at least about 20 percent of their original strength at threeweeks after implantation, with the suture mass being essentiallyabsorbed in the body within about 60 to 90 days post implantation.

Certain bioabsorbable elastomers may also be used to form theattenuation devices or fuses in accordance with the present invention.The elastomers can be melt-processed, for example by extrusion toprepare sheets, plugs or tubular structures. In one embodiment, thecopolymers can be injection molded to fabricate intricately designedparts, or compression molded to prepare films. For the details of suchmelt-processing techniques, see, for example, F. Rodriguez, Principlesof Polymer Systems, Chapter 12 (McGraw Hill 1970).

The bioabsorbable elastomers can also be solvent cast to prepare thinfilms. Solvent casting can be accomplished using conventional methodssuch as first dissolving the copolymer in a suitable solvent to make asolution, then casting the solution on a glass plate to make a film, andthen evaporating the solvent from the cast film. In another processingscheme, the copolymers can be lyophilized to prepare foams.Lyophilization can be accomplished by first dissolving the copolymer inan appropriate solvent, freezing the solution, and then removing thesolvent under vacuum. The set of appropriate solvents include p-dioxane.Lyophilization techniques to prepare films are described in Louis Rey,Aspects Theoriques Et Industriels De La Lyophilization (1964).

Certain bioabsorbable elastomers are disclosed in U.S. Pat. No.6,113,624, titled Absorbable elastomeric polymer, issued Sep. 5, 2000,the disclosure of which is incorporated in its entirety herein byreference. In accordance with the process disclosed therein, a two-step,one-reaction vessel, two-temperature process is utilized in which amixture of p-dioxanone monomer and p-dioxanone homopolymer, is formed atlow temperatures of from about 100° C. to about 130° C., preferably 110°C. The mixture is then reacted with lactide at temperatures from about120° C. to about 190° C. to form copolymers in which segments orsequences are composed of both p-dioxanone and lactide repeating units.These segmented copolymers are stated to be less crystalline than theblock or graft copolymers previously known in the art and, therefore,yield materials with good strength, but shorter BSR (“Breaking StrengthRetention”) profiles, faster absorption rates, much longer elongationsand lower stiffness than the block copolymers. A wide variety ofcopolymers of polylactic and polyglycolic acids are also known in theart, particularly for use with absorbable orthopedic screws andfasteners.

The ideal material can be optimized through routine experimentationtaking into account the attenuation device design and the desiredindwelling time period. Attenuation devices may be time rated, such as15 days, 30 days, 45 days, 90 days, 180 days or other as may be desired.The deflated and or partially dissolved attenuation device will betransurethrally expelled within a few days of the expiration of therated time period from the time of implantation.

Referring to FIG. 12, there is illustrated a side elevational schematicview of one embodiment of an intravesical removal system in accordancewith the present invention. This removal system is adapted to retrievethe inflatable attenuation device discussed elsewhere herein. Theremoval system 150 comprises an elongate tubular body 152 which extendsbetween a proximal end 154 and a distal end 156. Tubular body 152 isdimensioned to transurethrally access the bladder. In one embodiment,the removal system 150 is adapted for use in conjunction with standardurological cystoscopes (e.g. approximately 14–24 French), having minimumworking channels of approximately 1.8 to 6.0 mm. For this purpose,removal system 150 in one embodiment has an overall length ofapproximately 76 cm and a useable length of approximately 60 cm.

The tubular body 152 may be manufactured in accordance with any of avariety of techniques well understood in the catheter and other medicaldevice manufacturing arts. In one embodiment, tubular body 152 isextruded from a biocompatible material such as TFE, having an insidediameter of approximately 0.09 inches and a wall thickness of about 0.01inches.

The proximal end 154 of tubular body 152 is connected to a Y-adaptor158. Y-adaptor 158 carries a control 160 for controlling the retrievalsystem as will be described. Control 160 in the illustrated embodimentcomprises a thumb ring 162 which is slideably carried with respect to apair of finger rings 164. Axial movement of the thumb ring 162 withrespect to the finger rings 164 enlarges or retracts a retrieval loop166 extending distally from distal end 156 of tubular body 152.Retrieval loop 166 is adapted to surround the inflated attenuationdevice 66. In one embodiment, the loop 166 has an enlarged diameter ofabout 27 mm, and comprises a wire such as 0.016 inch diameter stainlesssteel cable wire.

In use, the loop 166 is opened once the distal end 156 of the tubularbody 152 has reached the bladder. The loop 166 is positioned around theattenuation device 66, and the proximal control 160 is manipulated totighten the loop 166 around the attenuation device 66. After theattenuation device 66 has been securely grasped by the loop 166, adeflating tube 168, preferably having a sharpened distal tip 169thereon, is distally advanced through the wall of the attenuation device66. Distal advancement of the deflating tube 168 may be accomplished bydistally advancing a proximal control, such as control 172. The distaltip 169 is in fluid communication with a connector such as a standardluer adaptor 170 through a central lumen (not illustrated), so that anempty syringe or other device may be connected to the connector 170 andused to evacuate the contents of the ensnared attenuation device 66. Asthe attenuation device 66 is deflated, the control 160 may bemanipulated to pull the collapsed attenuation device 66 into the distalend 156 of the tubular body 152. The removal system 150 having thereduced attenuation device 66 therein or carried thereby may betransurethrally removed from the patient.

A wide variety of modifications can be made to the foregoing removalsystem 150, within the spirit of the present invention. For example, theproximal controls 160 and 172 may be combined into a pistol grip orother configuration. Controller 172 or control 160 may additionallycontrol deflection of the distal end 156 of the tubular body 152, orcontrol rotation of the plane of the loop 166. In general, the removalsystem 150 preferably accomplishes the basic functions of enabling thelocation of the attenuation device 66, capturing the attenuation device,reducing the attenuation device in size and removing the attenuationdevice from the bladder. The capturing step may be accomplished byvisualizing the attenuation device through the urological cystoscope, orby “blind” techniques, such as, for example, light reflectance,impedance, suction, ultrasound, passive induced microchip, or themagnetic locator described in connection with FIGS. 21, 22, 23, below.

Referring to FIGS. 13 and 13A, there is illustrated a top plan view ofone embodiment of an attenuation device 180 in accordance with oneaspect of the present invention. The attenuation device 180 comprises aninflatable body 68 generally as has been described. An outer seam 78 maybe provided with a valve 80. In this embodiment, an inner seam 182defines a central region 184. The outer seam 78 and inner seam 182define a generally torodial-shaped inflatable container 68. The centralregion 184 may comprise either a membrane or a central opening,depending upon the desired performance characteristics. The center holemay assist in the placement and location of the attenuation devicewithin the bladder, permit additional baffling of the pressure waveswithin the bladder, minimize the attachment to the bladder wall bysurface tension between the attenuation device and the bladder wall, andallow for urine flow through the hole in the event that the attenuationdevice is in or near the bladder neck.

In one embodiment, illustrated in FIGS. 14 and 14A, the central region184 comprises a baffle 186. The baffle 186 comprises a membrane 188having a plurality of apertures 190 therein. In the illustratedembodiment, approximately nine round apertures 190 are provided, eachhaving a diameter of about 0.2 inches. Generally at least about 9apertures 190 are provided, and many embodiments include anywhere fromabout 1 to about 1000 apertures. The optimal number of apertures 190 andsum of the area of the apertures 190 compared to the total area of thebaffle 186 may be optimized depending upon the desired performancecharacteristics. Apertures may have any of a variety of configurations,such as round holes, irregular openings, slits or others.

The wave diffuser function of the baffle 186 is schematicallyillustrated in FIG. 15. A wave front 192 may be generated by any of awide variety of events, such as coughing, sneezing, laughing, physicalmovement, muscle spasms or others as is understood. Since urinecomprises essentially non-compressible water, and due to the low dynamiccompliance of the bladder the wave front 192 will propagate rapidlythrough the bladder to impact structures such as the trigone area andthe urethra. Apparent transient pressure spikes as high as 80 cm H2O orgreater can be experienced during normal activities. In addition toreducing the pressure caused by pressure events such as coughing, theattenuation devices discussed above can also provide a baffle thatdistributes the wave across the bladder distributing and reducing thefocused wave front that contacts the bladder neck.

If the attenuation device 180, having a baffle 186 is positioned withinthe bladder, the baffle 186 functions to disrupt the unitary progressionof the wavefront 192. The prediffusion wave front 192 is thusinterrupted into a plurality of post-diffusion wave fronts 194 by thebaffle 186. Although the sum of the resulting post-diffusion wave fronts194 is essentially equal to the prediffusion wave front 192, the greaterdispersion of force accomplished by the baffle 186 is believed by theinventors to reduce the apparent magnitude of the wave front 192 asexperienced by target tissue within the bladder.

As will be apparent in view of the foregoing, the baffle 186 may beconstructed in any of a variety of manners and still accomplish theintended result. Thus, although the attenuation device 180 illustratedin FIGS. 13 and 14 comprises a generally toroidal-shaped inflatablecontainer, any of a variety of other support structures may be utilizedto maintain the baffle 186 in a useable configuration. The support 196can comprise an inflatable tube, a resilient material such as nitinolwire, or other support structure as may be desired.

Certain embodiments of the present invention include a device that ismechanically in contact with the mucosal tissue of the bladder orurethra. The sensation caused by the mechanical contact causes nervereceptors to tighten the urethral muscles increasing urethralresistance, thus, reducing or eliminating incontinence events.

Referring to FIG. 16, there is illustrated a variety of shapes for theattenuation device 66, of the inflatable container variety. The devicesused in embodiments of the present invention may take many shapes. Insome instances it may be desirable for manufacturing purposes to havethe shape resemble dip-molded devices like condoms, surgical glovefingers, or children's toys. However, many other forms may providebetter performance, in particular for providing baffling of pressurewaves as well as attenuation of pressure spikes. Possible shapes for theattenuation devices include torroid like shapes, similar in form but notsize to donuts and inner tubes; spoked wheel forms; horseshoe-likeforms; mushroom-like forms; and banana-like forms.

The attenuation devices of the present invention can be dip molded orextruded in a plurality of biocompatible materials. Furthermore, theattenuation devices can be fabricated from a variety of multi-layercomposites or produced by a number of different manufacturing processes.Here, the designs of the attenuation devices are characterized byminimization and control of the gas and moisture vapor permeabilities inand out of the attenuation device.

The gas and moisture vapor permeabilities of any given material willvary depending on the conditions surrounding the material. For example,an attenuation device comprised of a certain material can have differentgas and/or moisture permeabilities within the bladder than at standardtemperature and pressure. In addition to exposure to urine, theintravesical environment includes exposure to pressure variations in therange of from about 0.05 psi to about 0.25 psi at rest, with transientpressure spikes as high as 2 psi or more. The body temperature isnormally about 98 degrees F. or greater, and the attenuation deviceresides in 100% humidity. Long term efficacy of the attenuation devicemay be compromised if there exists any fluid or vapor exchange throughthe wall of the attenuation device in situ. The relative impermeabilityof the wall under normal intravesical conditions is preferablyaccomplished without losing the compliancy of the attenuation devicewhich allows it to compress within folds of the bladder as is describedelsewhere herein.

In general, the wall of the attenuation device will comprise at leastone gas barrier layer and at least one moisture barrier layer. Any of avariety of gas barrier materials (e.g. polyvinylidene chloride, ethylvinyl alcohol, fluoropolymers, etc.), available in thin filmconstructions, may be implemented into the attenuation device design.These materials are generally relatively stiff, have a high moisturevapor permeability, and have low impact strength. Consequently, layeringthe film with flexible, high moisture barrier, high impact strengthpolymers is desirable.

A variety of relatively flexible materials, having high moisture barriercharacteristic and optionally high impact strength that can be formedinto thin film sheets include but are not limited to: polyamide,polyethylene, polypropylene, polyurethane, polyamide/polyestercopolymer, polystyrene/polybutadiene copolymer, etc. In one embodiment,at least one layer on, or the entire attenuation device comprises ablend of a barrier material and a flexible high impact strength material(e.g. polyurethane/polyvinylidene chloride, polyethylene/ethyl vinylalcohol, etc.).

The attenuation device typically has two or more layers or barriers. Forexample, the attenuation device can have a gas barrier layer and amoisture barrier layer. An additional layer may be included to enhancethe structural integrity of the attenuation device. In one embodiment,the attenuation device has an outer layer comprising a gas barrier andan inner layer comprising a moisture barrier. In another embodiment, theattenuation device has an outer layer comprising a moisture barrier andan inner layer comprising a gas barrier.

The attenuation device can have three, four, five, or more layers. Inone embodiment, the attenuation device has a gas barrier layer, amoisture barrier layer, and one or more layers composed of at least onehigh impact strength material. In another embodiment, the attenuationdevice has multiple gas barrier layers arranged in a nonconsecutivearrangement. In yet another embodiment, the attenuation device hasmultiple moisture barrier layers arranged in a nonconsecutivearrangement. With respect to those embodiments having multiple,nonconsecutive barrier layers, the other layers of the attenuationdevice can include high impact strength material layers and/or othertypes of barrier layers.

The overall thickness of the wall is preferably minimized, and willoften be no more than about 0.03 inches. Preferably, the wall will be nomore than about 0.006 inches, and, in some implementations, is no morethan about 0.003 inches thick. An outer layer may comprise a soft,conformable material such as polyurethane, EVA, PE, polypropylene,silicone or others, having a thickness within the range of from about0.0025 inches to about 0.025 inches. The adjacent barrier layer maycomprise EVOH, PVDC or other materials in a thin film such as from about5 microns to about 25 or 30 microns thick. If the attenuation device isfabricated by bonding two sides together, a bonding or tie layer may beprovided on the barrier layer. Tie layers comprising polyurethane, EVAor others may be used, having a thickness of preferably no greater thanabout 0.001 inches. Layers of less than about 0.0008 are preferred, andlayer thicknesses on the order of from about 0.0003 to about 0.0005inches are contemplated.

The layers of the attenuation device can be formed in any number of waysknown to those skilled in the art, including, but not limited to,lamination, coextrusion, dip molding, spray molding, or the like, etc.As discussed above, the layers of the attenuation device can be formedfrom various materials. With respect to those attenuation devices thatare formed by laminating two or more layers together, various differentlaminating techniques known to those skilled in art can be used,including, but not limited to, heating, solvents, adhesives, tie layers,or the like.

The material may not need to be elastomeric at all for the attenuationdevice to function. However, the materials chosen for use in embodimentsof the present invention are to be sufficiently flexible in thethickness ranges dictated by the selected designs. When the attenuationdevice is subjected to external pressures, the attenuation device'smaterial is able to transmit the pressure to the contained air orpressure management construct and respond sacrificially as one of themost compliant members of the urinary system.

FIG. 16A illustrates a toroidal embodiment, in which a plurality ofcentral spokes are provided. FIG. 16B illustrates a crescent or “C”shaped attenuation device. Any of a variety of spherical, oval,elliptical or other shapes may be utilized such as those illustrated inFIG. 16C, in which the greatest length dimension of the inflatedattenuation device is within the range of from about 1 to about 5 timesthe smallest cross-section. FIG. 16D illustrates a less arcuate varietyas shown in FIG. 16B. In general, the attenuation device 66 may take anyof a variety of forms which provides a sufficient volume to achieve thedesired attenuation function, and which will minimize or eliminate riskof loss or obstructing outflow through the urethra.

Referring to FIGS. 17A and 17B, there is illustrated anaxially-compressible mechanical bellows type attenuation device inaccordance with the present invention. Attenuation device embodiments ofthe present invention for absorbing transient pressure changes includediaphragmatic structures, rigid structures both shape changing and rigidwith a coating or a bellows or bellows-like structure that can dampenpressure waves in an organ, chamber or cavity of the body as stand aloneattenuation devices or as part of the wall or structure of the organ ofinterest. One embodiment of a mechanically assisted attenuation deviceis in FIGS. 17A and 17B. FIG. 17A is a mechanical bellows that is in anormally extended position. The pressure within the bellows is reducedsuch that the bellows normally retains its extended position, but willcompress when external pressure is exerted on it. The bellows could bemade from plastic or metal, such as, for example, titanium or stainlesssteel from Senior Flextronics, Inc. Sharon, Mass. The bellows may besealed, or covered in a material that allows for the reduction of airpressure within the structure.

This approach has the advantage for significantly greater change ofvolume with change of pressure. The theoretical limits of the air celldescribed herein can only be reduced approximately 25% of its volume,but this bellows system can contract to almost 90% of its volume.

The bellow attenuation device 200 comprises a membrane 202, which iscollapsible in an accordion fashion. The membrane 202 may beself-supporting, or may be provided with an internal or external frame.The frame may comprise any of a variety of structures, such as a simplespring aligned in parallel with the longitudinal axis of the bellow, orpivotably moveable structures such as an axially compressible wirepantograph as will be understood in the art.

Referring to FIG. 18, there is illustrated a mechanically-assistedattenuation device 210 in accordance with the present invention. In thisembodiment, a compressible tubular wall 212 having closed ends 214, 216is supported by a self-expanding tubular frame 218. Any of a variety ofself-expanding tubular or spherical frame structures may be utilized,such as “zigzag” wire frames well known in the abdominal aortic aneurysmgraft arts. Although the abdominal aortic aneurysm graft applicationgenerally requires a relatively high, radially outwardly directed force,the present application would preferably be compressible with arelatively low compressive force (i.e., low radial force). This may beaccomplished by using wires of smaller gauge, less wire per graft,leaving adjacent apexes unconnected to each other, or other technique toreduce the radial force of the wire cage. The wire cage or other supportstructure is preferably surrounded by a water impermeable membrane suchas a balloon. Pressure within such balloon may be lower than 1 atm.

Referring to FIGS. 19A and 19B, there is illustrated another layout forthe inflatable attenuation device 66 of the present invention. In thisembodiment, illustrated in FIG. 19A, a plurality of attenuation devices67 are connected by a common flow path 65, so that the plurality ofattenuation devices 67 can be inflated through a single fill port. Inanother embodiment, illustrated in FIG. 19B, a plurality ofself-expanding attenuation devices are connected by a suture, Nitinolwire, or other tether, thereby minimizing the crossing profile and/ormaintaining a constant crossing profile for an attenuation device of anydesired total inflated volume.

FIGS. 20–23 illustrate a magnetic locating system for enabling “blind”retrieval without the use of a cystoscope. To remove the attenuationdevice from the bladder, the removal system is inserted into the urethrafor intravesical capture, deflation, and extraction of the attenuationdevice. The removal system utilizes a magnet whose polarity and fluxpath is oriented in a manner to ensure predictable attraction andcoupling of a magnet-containing attenuation device to the removalsystem. The removal system is coupled back to the attenuation device,and the attenuation device may be punctured and deflated using the jawsof biopsy-like forceps (or other solution suitable for deconstructingthe device) located at the distal end of the removal system. In oneembodiment, residual gas may be passively vented into the bladder orthrough the retriever body. Once deflated the attenuation device may bewithdrawn through the urethra attached to the removal system or allowedto pass out of the bladder as part of the urine flow.

Thus, referring to FIG. 20, there is illustrated an attenuation device230 such as an inflatable balloon 229 as has been described previouslyherein. The attenuation device 230 is provided with a valve 232 and alocating element 234. Locating element 234 may be any of the variety ofstructures which enable location of the attenuation device 230,preferably without the need for direct visualization.

In the illustrated embodiment, the locating element 234 is one or moremagnets 236. In the embodiment illustrated in FIG. 21, the magnet 236comprises an annular ring, for surrounding the flow path 83. Acorresponding magnet 238 having reversed polarities from the polarity ofthe magnet 236 is provided on the distal end of a catheter 240. Theattractive forces of the opposing polarity magnets 236 and 238 willcause the catheter 240 to couple on to the attenuation device 230, asillustrated in FIG. 22, when the catheter 240 is positioned in thevicinity of the attenuation device 230.

Referring to FIG. 22, at least one lumen 242 places the attenuationdevice 230 in fluid communication with the catheter 240 when thelocating element 234 is coupled to the catheter 240. This lumen 242 maybe utilized to either introduce inflation media or remove inflationmedia from the attenuation device 230. In FIG. 22, the valve 232 is aball valve, which is biased in the closed orientation. However, themechanism and structures disclosed herein may be used on any of theother valves disclosed elsewhere herein. In one embodiment, illustratedin FIG. 22, a valve actuator 234 may be advanced distally through thelumen 242 to displace the valve 232 and enable infusion or removal ofinflation media. Following the desired volume of infusion or removal ofinflation media, the valve actuator 234 may be proximally retracted, toenable the valve to close under its own bias. See FIG. 23.

The opposing magnets 236 and 238 may be utilized solely as a locatingstructure, such that an additional locking element (not illustrated) maybe utilized to lock the catheter 240 on to the attenuation device 230.This may be desirable if the strength of the bond formed between the twomagnets is insufficient to keep the attenuation device 230 coupled tothe catheter 240 during the filling or removal steps. In addition,following deflation of the attenuation device 230, the catheter 240 willgenerally require a relatively strong coupling to the attenuation device230 to retrieve the attenuation device 230, as will be apparent to thoseof skill in the art in view of the disclosure herein.

In accordance with one aspect of the present invention, the removalsystem is provided with one or more ultrasound transducers near a distalend thereof. An air filled attenuation device should strongly reflect anultrasound signal, in a manner similar to the reflection achieved at anair-water interface. A removal system provided with a deflectable distaltip and ultrasonic capabilities should be able to navigate through thebladder to locate an attenuation device without the need forvisualization. The removal system may additionally be provided with agrasping element, such as two or more opposing mechanical graspers,and/or a vacuum lumen, for attaching to the surface of the attenuationdevice using suction. Once attached, the attenuation device can bepierced and transurethrally withdrawn.

In accordance with another aspect of the present invention, there isprovided an attenuation device that may assume multiple shapes duringthe course of its use. For example, the attenuation device may becompletely deflated for introduction and inflated to varying degreesafter introduction. The attenuation device may be adjusted through theinflation/deflation of secondary or multiple containment cells for suchpurposes as ballasting or the addition of a diagnostic, therapeutic orsignaling substance. This may occur through multiple uses of a single,or single uses of a multi lumen, multi ported structure or combinationsthereof.

In accordance with another aspect of the present invention, the deliverysystem and the removal system of the attenuation device or accumulatorare two separate instruments. In another embodiment, the delivery systemand the removal system are implemented using a single instrument. In yetanother embodiment, there is provided one instrument having differentdistal ends for the delivery system and the removal system.

In accordance with another aspect of the present invention, an endoscopemay be used to launch and retrieve the device (i.e. attenuation device,accumulator, etc.).

In accordance with another aspect of the present invention, the distaltip of the delivery system may be straight, pre-curved, malleable, orsteerable (e.g., by pull wires) in order to facilitate delivery and/orrelease of the device.

In accordance with another aspect of the present invention, theseparation of the attenuation device from the fill tube may beaccomplished using the wall of the urethra or neck of the bladder as amechanically resistant body.

In accordance with another aspect of the present invention, the deliverysystem may consist of a single tubular element, a series of concentrictubular elements, a series of non-concentric tubular elements, anextruded element, a spirally wound guidewire element, or any combinationof the aforementioned elements arranged in a manner to provide thedesired functions.

In accordance with another aspect of the present invention, irritationconcerns are addressed through the use of coatings or fillers tophysically or chemically modify the attenuation device in whole or partin order to modulate characteristics such as lubricity and the abilityto inhibit the deposition of materials present in the urinary tract. Forexample, substances such as sulfated polysaccharides may be used before,during, or after introduction to the patient. In addition, the use of aplurality of construction materials with unique surface properties mayalso be used for this purpose.

In accordance with another aspect of the present invention, theattenuation device includes a portal that spans the distance from theinternal aspect to the external aspect that allows for the location ofan erodable substance that would allow for the deflation ordeconstruction of the attenuation device after exposure to urinary tractconditions for a prescribed period of time. This approach may also beused for the programmed bolus release of single or multiple therapeutic,diagnostic or signaling substances from single or multiple chamberswithin the attenuation device.

In accordance with another aspect of the present invention, theattenuation device is equipped with a valve/port that is programmable,self-regulating or responsive to stimuli, which may or may not bephysiological. Telemetry, physical connection or remote signaling may beused to elicit a desired response.

In accordance with another aspect of the present invention, theattenuation device accepts, captures, and/or translates physical forceswithin the urinary tract to energize a site within the attenuationdevice for the positive displacement of substances outside the boundaryof the attenuation device in either continuous or bolus presentation.

In accordance with another aspect of the present invention, there isprovided a port/valve that is not associated with the sealing edge ofthe attenuation device.

In accordance with another aspect of the present invention, there isprovided an attenuation device that includes a thin, pliable safetytether 332 long enough to extend from the attenuation device and exitfrom the meatus. See FIG. 24. The tether can be constructed of acceptedmaterials such as those used in the manufacture of sutures, cathetersand may also possess anti-microbial properties. In one embodiment, thedistal end of the tether may be terminated with a lightweight pendant334 of sufficient bulk to prevent ingress of the entire tether into theurethra. During normal use, the pendant may be temporarily affixed tothe patient's pelvic region. The tether may be used to remove ordeconstruct the attenuation device, and the tether provides the patientwith the capability of instant removal of the attenuation device in theevent the patient feels compelled to extract the attenuation device.

In accordance with another aspect of the present invention, there isprovided an attenuation device that is a chambered structure consistingof multiple subchambers for multiple functions. See FIGS. 25 and 25A–C.The primary attenuation device 336 may or may not be fluidicallyconnected to the secondary device 338. The fluidic connection 340 alsoacts as a tether with sufficient service loop to allow the secondarydevice 338 to be placed into the urethra while the primary attenuationdevice 336 remains untethered in the bladder 63, located above the pubicbone 69. During a urinary pressure spike, gas within the primaryattenuation device 336 compresses proportionally with the external load.The compressed gas is then allowed to transfer to the secondary device338, dwelling in the urethra, and causing a proportional expansion ofthe secondary device 338. The design of the secondary device 338 directsexpansion in an outward radial direction, transverse to the longitudinalaxis of the urethra, thus augmenting the natural inward radialcontraction of the urethra. This type of “on demand” synchronousresistance augmentation may be much more effective than other forms ofpassive or patient controlled augmentation systems. Another benefit ofthis embodiment of the present invention is that the synchronous outwardradial forces may help to positionally stabilize the secondary devicewithin the urethra. Passive devices must maintain a constant retentioncapability (force or displacement of tissue) sufficient to resist themaximum expulsion forces at all times. This level of retention may leadto patient discomfort and cause long-term tissue damage.

With reference to FIG. 25B, compression force (Fcomp) 342 equals the sumof ingress force (Fingress) 344 and the egress force (Fegress) 346. Withreference to FIG. 25C, the intravesical pressure 348 exhibits a rapidrise time and a rapid decay time. The secondary device pressure 350exhibits a rapid rise time and a delayed decay time. FIG. 26 illustratesthe effect of an attenuation device on the intravesical pressure. Here,the intravesical pressure 352 with the attenuation device exhibitsdelayed rise and decay times and remains below the leakage pressure of80 cm H₂O. This is contrast to the intravesical pressure 354 whichexceeds the leakage pressure.

With reference to FIG. 27, in one embodiment, the attenuation device 66is anchored to the bladder wall 356. In another embodiment, shown inFIG. 28, the attenuation device 66 is part of a tranurethrally-placeddynamic compliancy measurement catheter 358. In other embodiments of thepresent invention, the attenuation device may resemble a smallthree-spoked automotive steering wheel, or a rotating toroidal spacestation. See FIG. 16A. The outer ring would contain the attenuationdevice; the inwardly radiating spokes would provide fluid conduits andmechanical support for the secondary device attachment. The attenuationdevice may also incorporate one or more shape holding super elastic wiremembers to aid in positional stability. The secondary device couldresemble the distal tip section of a small diameter angioplasty deviceand be affixed to the central hub.

In accordance with another aspect of the present invention, a secondarydevice inflation/deflation response can be design regulated. Forexample, it may be beneficial to inflate the secondary as quickly aspossible, but induce a response lag in the deflation/inflation cycle toprotect against a second cough, sneeze or sudden mechanical shock.

In accordance with another aspect of the present invention, there isprovided a pressure compensator or bladder trainer that can be implantedwithin a treatment site, such as, for example, the abdominal cavity, andbe hydraulically or pneumatically connected to the bladder or beinstalled as a component of the bladder wall. The device would beconstructed of a rigid external enclosure to shield the compressibleelements from abdominal forces. The function of this embodiment would benot only to manage the transvescular pressure in treatment of a clinicalinsult, but also to introduce pressure waves either outside or insidethe bladder in order to increase the muscle tone, compliance or affectthe neuromuscular elements of the bladder.

The embodiments of the present invention have been described for use inthe human anatomy. As understood by those skilled in the art, thepresent invention is not limited to human use; rather appropriatelyscaled versions of the inventions disclosed herein can be used toprovide clinical benefits to other animals, including but not limited tomammalian household pets.

Certain embodiments of the present invention provide significantadvantages over prior art devices. These advantages include but are notlimited to: significant reductions in bladder dysfunction relatedevents; the ability to retrain a bladder with other than normalcompliance; no patient interaction required to operate or maintain theattenuation device; patient is allowed to void in a normal fashion; noinfection conduit between the bladder and the distal end of the meatus;minimal sensation generated by the attenuation device; low cost tomanufacture; cost effective solution for patient when compared toexisting treatments; and ease of installation and removal for clinician.

In accordance with one aspect of the present invention, there areprovided devices and methods for measuring the dynamic compliance of thebladder. In one embodiment, a device can be used in combination with thefill tube/introducer to measure the dynamic compliance of the bladder.One lumen of the fill tube can be used to rapidly inflate the device,while pressure measurements of the bladder are made via a second lumen.In one embodiment, the volume is expanded by at least about 30 cc or 50cc up to as much as 200 cc in a time period of from about 0.5 to 10seconds to measure the dynamic compliance of the bladder.

In accordance with another aspect of the present invention, there areprovided methods and devices for the restoration of dynamic complianceof the bladder by retraining the bladder tissue by introducing pressurewaves at a prescribed place and with prescribed characteristics.

In accordance with another aspect of the present invention, there areprovided methods and devices for the programmatic delivery of clinicaltherapeutics in association with defined pressure events. The presentinvention could be added to other intravesical devices, such as Foleycatheters, intravesical infusers, such as those described inWO1998US0021368, filed Oct. 9, 1998, titled intravesical infuser (thedisclosure of which is incorporated in its entirety herein byreference), or the ends of urethral stents to facilitate delivery, totreat multiple symptoms, or to enhance the performance of either device.For example, the attenuation device could work in combination withintravesical infusers, to time the release of medications relative topressure events within the bladder.

In accordance with another aspect of the present invention, there isprovided an atraumatic method of measuring intravesical pressure withoutthe need for any external connection by placing a pressure transducerand telemetry device within the attenuation device. This secures thetransducer within the bladder and prevents the need to attach thetransducer to the bladder wall.

Embodiments of the present invention are not limited to intravesicaldevices, but also include devices and methods for controlling pressuretransients in other organs of the body, as will now be discussed.

With reference to FIG. 29, which shows a tubular attenuation device 66in a vessel 360, one embodiment of the present invention is intended foruse in cardiovascular applications to modulate pressure waves to protectthe heart and/or the vasculature from being damaged due to exposure tothe pulsitile forces of normal or extreme physiological events byreducing mean arterial pressure, systolic pressure and or diastolicpressure. An attenuation device can be placed in the wall of the heart,within a major artery, or within the left atrial appendage of the heart(see FIGS. 30A and 30B) to reduce risk of renal failure, stroke, heartattack, blindness. With reference to FIG. 30A, in one embodiment, an aircell attenuation device 66 is positioned in the left atrial appendage ofthe heart. With reference to FIG. 30B, in one embodiment, a bellows-typeattenuation device 66 is positioned in the left atrial appendage.

An attenuation device can be placed on or within the right side of theheart or in a pulmonary artery to reduce symptoms of primary permanenthypertension. An attenuation device can also be placed on the venousside of the vasculature system, such as within the wall of the vena cavaor attached to a Greenfield filter within the vena cava to preventportal hypertension and/or esophageal varicies. An attenuation device,such as an air cell, can be attached to or encompass a stent forplacement within the vasculature.

In another embodiment, the attenuation device can be used in the gallbladder to modulate pressure contained therein. Pressure in the gallbladder may lead to undesired events such as the formation of stones orpain for the patient. An attenuation device can also be placed in theesophagus on the end of an NG tube to limit spasm. With reference toFIG. 31, an attenuation device 66 can be placed in the bowel 364 totreat irritable bowel syndrome, minimize crons disease, cramping, or anyother disorder resulting from peristalsis.

In another embodiment, the attenuation device is used in the field ofopthamology to support cranio-facial tissue during healing after atraumatic event or intraoptically as therapy for acute angle closureglaucoma. In yet another embodiment, the attenuation device is used inthe field of orthopedics as an implantable or external system to protectagainst pressure waves and control the location of a healing bone aftera traumatic event. In still another embodiment, the attenuation deviceis used in the field of otorhinolaryngology for the management ofpressure waves in the sinus cavities, including in and around the ears,the nose and the throat. In another embodiment, an attenuation device isplaced in the lung to treat disorders such as, for example, asthma,bronchio spasms or prevent damage from coughing in fragile lung tissuesin emphysema sufferers, etc. In yet still another embodiment, anattenuation device is used to prevent Central Nervous System (“CNS”)problems such as, for example, head trauma, cerebral edema,hydrocephalus, etc. Here, the attenuation device can be placed in theepidural pocket under the skull.

In accordance with one aspect of the present invention, there areprovided air cell-like attenuation devices that are placed in thebladder and/or other organs of the body and filled with or comprise oneor more compressible substances to provide pressure compensation.Additionally, active, programmable pressure compensators or generatorsare envisioned to monitor pressure events, respond in a predeterminedfashion, and record or transmit that information outside the body.Additionally, a reliable, maintenance-free therapeutic delivery systemis described to programmatically release or distribute an agent into anorgan of the body using an erodable or deformable support matrix ormaterial of construction, and/or a programmable or responsive valvingsystem.

In accordance with one aspect of the present invention, there isprovided a compressible attenuation device having a valve that permitsfilling of the attenuation device through a filling device and yetresists deflation and/or additional filling of the attenuation deviceafter the filling device is removed. In one embodiment, illustrated inFIGS. 36 and 37, the valve 80 is formed by two parallel welds 281, 283at the interface between two complementary surfaces—namely, the outercover 280 and the underlying layer 284. The valve 80 is in effect acollapsible airflow passageway that remains in the collapsed positionwhen the filling device is removed, thereby preventing deflation whenthe pressure within the attenuation device 66 is greater than thepressure immediately outside the attenuation device and preventing theadditional filling of the attenuation device 66 when external pressureis greater than the pressure within the attenuation device 66. The outercover 280 and the underlying layer 284 function as two flat sheets thatstick together regardless of the relationship between the internalattenuation device pressure and the immediate external pressure. In oneembodiment (not shown), one or more adhesive martials or general lockingmechanisms known in the an of medical device design can be used to shutthe value 80 upon removal of the filling device. It should be noted thatonce the filling device enters the valve at the entry point 82, theattenuation device can be released and/or filled at any point inside ofthe entry point 82, including but no: limited to the interface 282between the valve 80 and the inside of the attenuation device 66. Thevalve of the present embodiment can be constructed according to thedisclosure provided by U.S. Pat. No. 5,144,708, titled check valve forfluid bladders, issued Sep. 8, 1992, the disclosure of which isincorporated in its entirety herein by reference.

In another embodiment, illustrated in FIG. 38, the valve 80 includes twoduckbill structures that face opposite each other, thereby permittingfilling of the attenuation device through a filling device whileresisting deflation and/or additional filling of the attenuation deviceafter the filling device is removed. The valve 80 generally comprises atubular wall 81, having an aperture 82 in communication with a flow path298. The valve has two sets of first and a second duck bill valveleaflets 86, 88, 290, 292 that are attached to the tubular wall 81. Uponremoval of the inflation media source, the inflation media withinattenuation device 66 in combination with natural bias of the leaflets86 and 88 cause the leaflets to coapt, thereby preventing effluent flowof inflation media through the flow path 83. In addition, the naturalbias of the leaflets 290 and 292 cause the leaflets to coapt, therebypreventing the additional influx of media. It should be noted that theinternal section 294 of the tube will have a pressure equal to theinternal pressure of the attenuation device, whereas the externalportion or flow path 298 will have a pressure equal to the immediateexternal pressure. A middle or neutral section 296 of the tube isdefined by the tubular wall and the two oppositely facing duckbillstructures defined by leaflets 86, 88, 290, 292.

In accordance with another aspect of the present invention, there isprovided an implantable self-inflating pressure attenuation device thatcan inflate from a first, deflated configuration to a second, at leastpartially inflated configuration. Various transformable mediums can beused to inflate the housing of the attenuation device from a deflatedconfiguration to at least a partially inflated configuration.

With reference to FIGS. 47A–47C, in one embodiment, the transformablemedium comprises a first reactant 432 and a second reactant 434. Here,the implantable self-inflating pressure attenuation device 430 (shown inits first, deflated configuration) generally comprises a first reactant432 and a second reactant 434, which are physically separated from eachother. When the first reactant 432 comes into contact the secondreactant 434, a chemical reaction occurs within the attenuation device430, thereby causing the attenuation device 430 to transform into atleast a partially inflated configuration (not illustrated).

With reference to FIG. 47A, in one embodiment, the first reactant 432 iscontained within a balloon or container 436 that is entirely containedwithin and free to move within the attenuation device 430. The container436 is generally impermeable to reactants 432, 434, and can comprise anysuitable material known to those skilled in the art. The suitability ofa material for the container 436 will depend on the chemicalcharacteristics of the reactants 432, 434. In another embodiment,illustrated in FIG. 47B, the reactants 432, 434 are compartmentalizedand separated within the attenuation device 430 by a wall 438. The wall438 is generally impermeable to reactants 432, 434, and can comprise anysuitable material known to those skilled in the art. The suitability ofa material for the wall 438 will depend on the chemical characteristicsof the reactants 432, 434. In yet another embodiment, shown in FIG. 47C,the attenuation device 430 has a crease 440. The crease 440 separatesthe reactants 432, 434, and thereby prevents the inflation/expansionreaction from occurring until such inflation/expansion is desired andtriggered by the user. In still another embodiment (not illustrated),the reactants 432, 434 are separated within the attenuation device 430by a peelable bond, fold, and/or the like, known to those skilled in theart.

In one embodiment, the medium capable of transformation comprises gasgenerating compositions. Various compositions can be used to generategas in accordance with this invention. One class of compositions is thecombination of a base and an acid to produce carbon dioxide. The acidand base are combined in dry form and rendered reactive only whenco-dissolved in water. Examples of suitable bases are water-solublecarbonate and bicarbonate salts, nonlimiting examples of which aresodium bicarbonate, heat treated sodium bicarbonate, sodium carbonate,magnesium carbonate, potassium carbonate, and ammonium carbonate.Nonlimiting examples of suitable acids are citric acid, tartaric acid,acetic acid, and fumaric acid. One presently preferred composition is adry mixture of sodium bicarbonate and citric acid. Compositionscontaining more than one acid component or base component can also beused.

Gas generation can be initiated various ways, such as, for example,contact with a fluid, temperature change, ignition, pH change, etc. Inone embodiment, the amount of gas generated is equal to the amount ofvolume dissipated through the air cell, thereby allowing for constantvolume device until the gas generating materials are exhausted.

The amount and rate of gas production can be controlled by certainfactors, such as, for example, the amount of reactive materials orreactants, the amount of gas entrapped in the structure, or thesolubility of one or both of the chemicals in water, etc. In oneembodiment comprising a wick and tablet systems, the available water asdelivered by the wick to the tablet dissolves only a limited amount ofthe reactants and resulting reaction product(s). The reaction is thuslimited by the solubility of the chemicals in the limited amount ofavailable water. The rate of water delivery thereby controls thereaction rate. Some examples of the solubility of suitable reactionchemicals per 100 grams of water are as follows: sodium bicarbonate,about 10 g; citric acid, about 200 g; tartaric acid, about 20 g; andfumaric acid, about 0.7 g. The limited solubility and limited waterdelivery rate through the wick make it unnecessary to keep the acid andbase separated either before or during use of the infusion device.

It is further understood that a catalyst, another chemical species orone of the byproducts of the reaction can propagate the reaction andincrease its speed. In the case of sodium bicarbonate and citric acid,the byproducts are carbon dioxide, sodium citrate, and water. A verysmall amount of water, such as, for example, 0.1 to 0.5 ml, can be usedto start the reaction by dissolving the sodium carbonate and citricacid. Since water is produced in the reaction, the reaction speedincreases until all of the reactants are exhausted.

As a manufacturing aid, it may be desirable to add inert agent(s) to thereactant composition to aid in the tableting process and to keep thetablet intact during and after use. Examples of suitable tableting aidsinclude but are not limited to polyvinyl pyrrolidone and anhydrousdibasic calcium phosphate, sold by Edward Medell Co. (Patterson, N.J.,USA) as EMCOMPRESS.RTM. Tableting aids can be eliminated for certaincompositions with no loss of performance. One such composition is themixture of sodium bicarbonate and citric acid.

Chemical compositions that produce oxygen or other gases can also beused. A composition to generate oxygen in the presence of water isdisclosed in U.S. Pat. No. 4,405,486, titled Method for Preparinggranulated perborate salts containing a polymeric fluorocarbon, issuedSep. 20, 1983, the disclosure of which is incorporated in its entiretyherein by reference. The controlled rate of wicking water into such atablet, and the limited solubility of the constituents can control therate of oxygen release in a manner similar to that of carbon dioxide inthe systems described above.

In another embodiment, the medium capable of transformation comprisesperoxide and/or superoxide chemical systems. In certain embodiments, gasis generated by drawing an aqueous solution of a peroxide or superoxideinto an absorbent tablet that contains an enzyme or catalyst whichpromotes the decomposition of the peroxide or superoxide todecomposition products including oxygen gas. In another embodiment, asolid peroxide or superoxide can be incorporated into the tablet, withoxygen generation being initiated by contact of the peroxide orsuperoxide with water. Hydrogen peroxide, for example, decomposes intowater and oxygen, providing no hazardous reaction products afterinfusion of the liquid has been completed. Metal peroxides, such as, forexample, lithium peroxide, sodium peroxide, magnesium peroxide, calciumperoxide, and zinc peroxide, etc., react with water to produce the metalhydroxide and hydrogen peroxide, which then decomposes into water andoxygen. Superoxides, such as, for example, sodium superoxide, potassiumsuperoxide, rubidium superoxide, cesium superoxide, calcium superoxide,tetramethylammonium superoxide, etc., react with water to produce themetal hydroxide and oxygen gas directly. It will be noted that theproduction of hydrogen peroxide itself is particularly preferred.

In one embodiment, a suitable tablet contains a water absorbent materialto facilitate the wicking action, and the enzyme or catalyst in systemswhere enzymes or catalysts are used. Examples of water absorbents usefulfor this purpose include superabsorbent polymers, reconstitutedcellulosic materials, compressed zeolite powder (Types 13X and 4A, bothunactivated), etc.

One example of a suitable enzyme is catalase. Lyophilized catalases aregenerally preferred. Catalysts effective for the decomposition includemetals deposited on high surface area substrates, such as, for example,alumina, activated carbon, etc. Examples of suitable catalysts includeplatinum, palladium, silver, etc.

Chemical reactants can also be used rather than enzymes or catalysts todecompose hydrogen peroxide. Examples of such reactants include but arenot limited to potassium permanganate, sodium hydroxide, etc. It shouldbe noted, however, that there are safety concerns associated withpotassium permanganate and sodium hydroxide.

As between enzymes and catalysts, enzymes provide a cost benefit forsingle-use systems. For reusable systems, however, catalysts aregenerally preferred. One significant advantage to the use of a hydrogenperoxide system with a catalyst is the ability to regenerate the systemby drying out the tablet and adding more hydrogen peroxide solution tothe water reservoir. Regeneration in this type of system is thus easierthan regeneration of an absorbent tablet for a system that requiresadsorbed gas.

In another embodiment, the medium capable of transformation compriseschemical reactants that are used effectively to generate a gas to push afluid from an infusion pump. In order to generate carbon dioxide, two ormore reactive chemicals are mixed that, upon reaction, generate a gas.Preferably, one of the reactants is provided in liquid form, i.e., aliquid chemical, a solution, or the like, and another one of thereactants is provided as a solid. Either the liquid or the solid maycomprise more than one reactive chemical. However, in one preferredembodiment, each of the liquid and the solid contain only one reactivespecies.

Carbon dioxide is generally quite inert and safe at low concentrations.However, other gases could also be used, provided they are relativelyinert and safe. For the purposes of the following discussion, it will beassumed that carbon dioxide is to be generated. As mentioned above, togenerate the gas, at least two reactants are caused to come intocontact. For ease of reference, the reactants will be referred to hereinas a first reactant and a second reactant or a solid reactant and aliquid reactant, and particular sets of reactants will be referred to asreactant sets.

First Reactant: Preferably, the first reactant is selected from a groupconsisting of carbonates and bicarbonates, particularly, Group I and IImetal carbonates and bicarbonates (the “carbonate”). For example, in oneembodiment, preferred carbonates include sodium bicarbonate, sodiumcarbonate, magnesium carbonate, and calcium carbonate. However, sodiumbicarbonate, sodium carbonate and calcium carbonate are highlypreferred, with sodium carbonate (or soda ash) being the most highlypreferred. One desirable feature of sodium carbonate is that it iseasily sterilizable. For example, sodium carbonate can be sterilizedwith heat, such as through autoclaving. This is preferable, since theinfusion devices for use with the invention are designed for human useand it is safer to ensure that all of the components are sterile whetherit is expected that they will come into contact with the patient or not.Other reactants that are sterilizable with heat, ethylene exposure, orexposure to ionizing radiation are equally useful.

The carbonate can be either used as a solid reactant or can be dissolvedin a solution to form a liquid reactant. In one preferred embodiment,the carbonate is used as a solid. The reason for this choice is that thecarbonates are all solids and some are only sparingly soluble in water.

Second Reactant: The second reactant is preferably an acid. Preferably,the acid is selected from the group consisting of acids, acidanhydrides, and acid salts. Preferably, the second reactive chemical iscitric acid, acetic acid, acetic anhydride, or sodium bisulfate. Usuallythe second reactant is used as the liquid reactant. However, in the caseof citric acid and sodium bisulfate, for example, the second reactantcan also be the solid reactant. Nevertheless, the second reactant isgenerally more soluble in water than the first reactant and is,therefore, used to form the liquid reactant.

Reactant Sets: A reactant set is based upon a variety of considerations.For example, the solubility of the first and second reactants areconsidered to determine which reactant should be used as the solid orliquid reactant. Also considered is the product of the reaction and itssolubility. It is preferred that the products be CO2 gas and a solubleinert compound. Once these factors are considered, appropriate reactantsets can be constructed. For instance, in one embodiment, reaction setssuch as those shown in Table I are preferred.

TABLE I Solid Reactant Liquid Reactant Sodium Carbonate Citric AcidCalcium Carbonate Acetic Acid Magnesium Carbonate Citric Acid

Additional details may be found in U.S. Pat. No. 5,992,700, titledcontrolled gas generation for gas-driven infusion devices, issued Nov.30, 1999, and U.S. Pat. No. 5,588,556, titled method for generating gasto deliver liquid from a container, issued Dec. 31, 1996. Both of thesepatents are hereby incorporated by reference herein and made a part ofthis specification.

In another embodiment, the method of producing gas is entrappedpressurized gas in a sugar or a porous molecular sieve. Generally, gasis liberated when the structure comes in contact with a fluid.

In accordance with another aspect of the present invention, there isprovided a method of delivering the implantable self-inflating pressureattenuation device 430 into the treatment site, such as, for example,the bladder. With reference to FIGS. 48A–48D, in one embodiment, thedelivery system 450 includes a bifurcated delivery tool 452 and adelivery cannula 454. The tool 452 has a fork-like shape and can beextended out and retracted into the cannula 454. As illustrated, thebifurcations of the tool 452 are spaced so as to squeeze or pinch thedevice 430, thereby separating a first portion 444 of the attenuationdevice 430 from a second portion 446, and thereby separating a firstreactant 432 from a second reactant 434. Because the reactants 432, 434do not come into contact with each other, the device remains in itsdeflated state, thereby facilitating the procedure of delivering theattenuation device 430 to the treatment site, such as, for example, thebladder. In one embodiment, shown in FIGS. 48B and 48C, first and secondportions 444, 446 of the deflated attenuation device are wound aboutitself along the axis of the tool 452, thereby minimizing the volume ofthe attenuation device 430, and thereby facilitating the delivery of theattenuation device 430 into the treatment site.

In accordance with another aspect of the present invention, there isprovided a method of improving the dynamic compliance and/orcontractility of the bladder.

Histology: The muscoa of the bladder is composed of transitionalepithelium. Beneath it is a well-developed submucosal layer formedlargely of connective and elastic tissues. With reference to FIGS. 40Aand 40B, the connective and elastic tissues of the bladder wallgenerally comprise mucosa 394, elastin 396, collagen 398, and muscle400.

With reference to FIG. 40A, as in most tissues, collagen 398 is arrangedas a coiled or complex helical material within the bladder wall. Whilecollagen 398 itself is not very elastic (distensible), the coiledconfiguration allows expansion of the collagen bundle. When the bundleis extended (see FIG. 40B), the uncoiled collagen length becomes thelimiting size. It is at this point that tension rises rapidly, analogousto the twisting of several strands of rope. When twisted, the combinedstrands shorten. The combined strands can be lengthened by untwistingwithout stretching any individual strand. As in other tissues, as thepatient ages the elastin 396 converts to collagen 398, reducing thecompliance of the bladder 63. External to the submucosa is the detrusormuscle 400, which is made up of a mixture of smooth muscle fibersarranged in a random, longitudinal, circular, and spiral manner.

Physiology: The functioning of the bladder includes contributions fromeach of the layers of the bladder 63 described above. One method ofunderstanding the properties of the bladder over time is to evaluate acystometrogram, which, in one embodiment, is generated by reasonablyslow continuous filling of the bladder 63. FIG. 41 illustrates a typicalcystometrogram. Initially, during Phase 1402 when the bladder 63 isempty, elastic elements are not stretched. Here, the bladder is in acollapsed state and none of the materials within the wall are expanded.Accordingly, there will be no tension within the wall and pressurewithin the bladder will be relatively low. During Phase II 404, as fluidfills the bladder, the walls unfold and elastic structures start tostretch. Now there is some tension and bladder pressure rises. As thebladder continues to fill, and the elastic tension continues toincrease, the radius increases as well. From the Law of Laplace for asphere, (P=2T/R), it will be noted that in order for pressure to remainconstant, the proportion between tension and radius must remainconstant. During Phase III 406, as the bladder capacity is reached,collagen and/or other less elastic materials have become unfolded andare themselves subject to stress. Since their modulus of elasticity isless than that for elastin and for the other elements on stress up tothis point, the wall tension rises quickly and bladder fluid pressurerises steeply. A slight increase in volume or radius will now produce arapid change in pressure. As this stretch occurs, neurological factorsapply as afferent impulses from the bladder in response to stretch beginto occur with a significant frequency.

Therapeutic Benefits, Methods of Improving the Dynamic Compliance of theBladder, Methods of Improving the Contractility of the Bladder: Based ondemonstrations by Solace, Inc. it is believed that the removal of highfrequency, repetitious insults to the bladder wall for a 5 day to 180day period of time increases the dynamic compliance of the bladder andreduces symptoms of incontinence by: precluding/reducing the stretch ofelastin fibers; reducing of the conversion of elastin fibers intocollagen; allowing the “stretched” muscles of the bladder wall toshorten, thereby improving compliance and bladder wall contractility;removing pressures exerted on the pelvic floor and connective tissues,allowing retraining and healing, increasing urethral resistance; placingthe attenuation device in the bladder provides passive resistance to thebladder neck and bladder wall, allowing the muscles to strengthen. Theseand other therapeutic benefits could last up to about 30 days to aboutone year. One additional benefit of attenuation and/or improving bladdercompliance includes improved flow during voiding (i.e. method ofimproving flow during voiding by “smoothing” the pressure within thebladder). Abdominal straining, resulting in a raised abdominal pressurePabd and, therefore, an increased intravesical pressure is not oftenemployed in normal voiding, nor is it usually as efficient as detrusorcontraction in producing voiding. If, however, the detrusor contractionis weak or absent abdominal straining may be the only available way ofvoiding and may then become of primary importance.

The detrusor pressure is not by itself a measure of the strength of thedetrusor contraction. A satisfactorily contracting detrusor can produceeither a high detrusor pressure and a low flow-rate, or a low pressureand a high flow-rate. The tradeoff between the pressure generated andthe flow produced results from the force/velocity relationshipcharacteristic of any contracting muscle. Consequently, for patientswith low dynamic bladder compliance, any pressure changes during flowcan significantly decrease flow rates. For patients that have weakdetrusor contractions and/or those that “bear down” for force urine outof the bladder, sometimes referred to “Val Salva voiders,” there isgreat pressure fluctuations within the bladder during voiding, resultingin reduced flow rates. By attenuating pressures within these patientsvia an attenuation device, improved flow can be achieved.

Another benefit of attenuation and/or improving bladder complianceincludes improved urethral closure pressures. Changes in abdominalpressure affect not only the intravesical pressure but also the urethra,proximally by direct mechanical action. The result is that when theabdominal pressure rises, as during straining or a cough, the urethralpressure discussed above also rises. The maximum urethral closurepressure therefore does not diminish, and may even increase. Thisrepresents a natural defense against leakage during stress. This processis enhanced by the attenuation of intravesical pressures within thebladder, with full exposure of the urethra to increased abdominalpressures.

Another benefit of attenuation and/or improving bladder complianceincludes improving the symptoms of benign prostatic hypertrophy (“BPH”).As the prostate enlarges, flow rates are reduced and residual volumesincrease. The symptoms of low flow are increased as the increasedintravesical pressure causes a decrease in the compliance of the bladderwall, bladder muscles elongate, elastin converts to collagen in the mostsevere cases), making it even more difficult for the bladder to “push”the urine through the restricted opening of the prostate. As thiscascade continues, the symptoms of benign prostate hyperplasia increase.Placement of an attenuation device in the bladder reduces symptoms ofBPH by improving flow, increasing the compliance of the bladder wall,removing high pressure insults to the bladder wall, and allowing thebladder wall muscles to shorten, all permitting the bladder to moreeffectively “push” the urine through the urethra and prostate. In oneembodiment, the attenuation device in the bladder reduces the symptom ofBPH by attenuating increases in pressure within the bladder byreversibly reducing its volume in response to the pressure increases.For example, in one embodiment, the attenuation device reduces itsvolume by at least 5%. In another embodiment, the attenuation devicereduces its volume by at least 10%. In yet another embodiment, theattenuation device reduces its volume by at least 25%.

Conformable Device: Patients generally experience pain and irritationwhen any foreign object is either wholly or partially in the bladder orbladder neck. With reference to FIG. 42, this pain can occur when thebladder or bladder neck has collapsed onto the foreign object 408,perhaps within a fold of the bladder; the pressure exerted on thebladder wall by focal points on the device creates pain and irritation.This pain is typically more acute when the patient is in the horizontalposition.

With reference to FIG. 43, to eliminate pain and irritation of thebladder and bladder neck when the bladder collapses on to any device(wholly or partially in the bladder and bladder neck), the shape of theattenuation device 410 can change to conform to the bladder wall inorder to maximize the surface area of the attenuation device in contactwith the bladder wall so as to dissipate the pressure over as large asurface area of the bladder wall as possible, and thereby prevent thefocal points that cause trauma, pain, or irritation to the bladder. Inone embodiment, the attenuation device has a compressible wall, therebyresulting in a conformable device where the medium (e.g., gas) withinthe device can move out of a fold in the bladder wall to reduce trauma.Examples of such attenuation devices 410 include but are not limited to:attenuation device having 15 cc of air in a container that is capable ofholding 30 cc of volume; Foley catheter or other catheter having aninflatable anchoring balloon; drug delivery infuser; J stent; etc.

FIGS. 39A–D illustrate attenuation (i.e. pressure reduction) withvarious attenuation device air volumes. The data for these graphs weregenerated using a bench top bladder simulation program. Here, themaximum spike pressure is 2.0 psi. The spike event duration isapproximately 40 mS, which is approximately equivalent to the durationof a coughing or sneezing event. With reference to FIG. 39A, a test wasconducted with a 250 mL rigid plastic container filled with syntheticurine. A regulated pressure of 2.0 psi was introduced into the containervia a controlled solenoid valve. A pressure transducer detected thepressure rise. Here, the pressure rise time (Tr) of the containerpressure 422 to reach 2.0 psi was approximately 40 msec. With referenceto FIG. 39B, a similar test was conducted on a 250 mL rigid plasticcontainer. Here, an attenuation device filled with 15 mL of air wasplaced inside the container willed with synthetic urine. Here, the Tr ofthe container pressure 424 to reach 2.0 psi was approximately 195 msec.Thus the attenuation device slowed the rise time by 4.8×. During thespike event (i.e. when time equaled 40 msec), the pressure inside thecontainer reached 0.7 psi (vs. 2 psi), resulting in a 65% reduction ofpressure vs. baseline. With reference to FIG. 39C, a similar test wasconducted; the only difference being that the attenuation device wasfilled with 25 mL of air. Here, the Tr of the container pressure 426 toreach 2.0 psi was approximately 290 msec. Thus the attenuation deviceslowed the rise time by 7.25×. During the spike event (i.e. when timeequaled 40 msec), the pressure inside the container reached 0.5 psi (vs.2 psi), resulting in a 75% reduction of pressure vs. baseline. Withreference to FIG. 39D, a similar test was conducted; the only differencebeing that the attenuation device was filled with 30 mL of air. Here,the Tr of the container pressure 428 to reach 2.0 psi was approximately340 msec. Thus the attenuation device slowed the rise time by 8.5×.During the spike event (i.e. when time equaled 40 msec), the pressureinside the container reached 0.4 psi (vs. 2 psi), resulting in a 80%reduction of pressure vs. baseline.

FIGS. 44A–D shows pressure vs. time curves generated by a bench topbladder simulator. FIG. 44A shows the baseline pressure-time curvewithout an attenuation device. FIG. 44B shows the pressure-time curvewith an attenuation device having a 15 cc air volume. FIG. 44C shows thepressure-time curve with an attenuation device having a 25 cc airvolume. FIG. 44D shows the pressure-time curve with an attenuationdevice having a 30 cc air volume.

Algorithm(s) for Measuring Leak Point Pressures: Typical measurement ofa patients leak point pressure is taken with pressure catheters in thebladder and in the rectum. The patient tightens the abdominal and pelvicmuscles (valsalva) to increase the external pressure exerted on thebladder. At the time when the test administrator identifies visuallythat leakage has occurred, a button is pressed, and the most recentpressure data points are recorded. Typical urodynamic equipment in usetoday measures 2 to 35 data points per second. Given the time delay fromwhen leakage occurs and when leakage is evident to the testadministrator, and the fact that pressure decreases when leakage occurs,one embodiment of a more accurate method of measuring leak pointpressure involves measuring pressure at the rate of 1000 pts per second,and programming or setting a computer to look at the prior 5/3/2/1second(s) and to look for the peak-generated pressures when theclinician presses the “leak” button (i.e. a button on or incommunication with the computer that the clinician pushes upon seeing ordetecting leakage).

In accordance with another aspect of the present invention, there isprovided a method of attenuating pressure changes in the bladder byintroducing one or more low permeability gases and/or fluids with highervapor pressures into an attenuation device. A lower permeability andhigher vapor pressure gas or fluid usually has a higher density than airor water, respectively. The solubility of the gas or fluid in urine iscommonly very low. With reference to FIG. 49, the illustrativeembodiments described herein show an attenuation device 66 with one highvapor pressure gas or fluid. However, it will be understood that theattenuation device 66 can have one or more high vapor pressure gasesand/or fluids, or combinations thereof. Outside the body, theatmospheric pressure (P_(a)) is equal to the partial pressure of air(P_(Air)). The pressure within the bladder (P_(b)) is approximatelyequal to P_(a); however, in practice, P_(b) is slightly higher P_(a).For example, if P_(a) is 14.7 psi or 1 atm, then P_(b) can beapproximately 14.85 psi (i.e. 14.7 psi+0.15 psi). There is a usually apressure gradient from P_(b) to P_(a) within the tissues 464 of the bodymoving from the walls 466 of an individual's bladder 468 to thesurrounding atmosphere 460 outside the skin 462. Since P_(b) is greaterthan P_(a), the pressure gradient results in the transfer of gases fromthe inside the body, such as, for example, from within the bladderoutward through the pores in the skin 462 of an individual. The totalpressure within the attenuation device (P_(T)) (i.e. within the outerwall 470 of the attenuation device 66) is equal to the sum of partial orvapor pressures of the high vapor pressure gas or fluid (P_(HD)) andP_(Air).

With reference to FIG. 49, in one embodiment, the attenuation device 66comprises an outer wall 470 and a high vapor pressure gas or fluid thatgenerally has low permeability through the outer wall 470. In oneembodiment, the wall 470 comprises a material, such as, for example,polyurethane, that is characterized by low permeability for the highvapor pressure gases and vapors and moderate to high permeability forair. Examples of suitable high vapor pressure gasses or fluids include,but are not limited to: sulfur hexafluoride hexafluoroethane;perfluorocarbons ranging from perfluoropropane, perfluorobutane,perfluoropentane, perfluorohexane, perfluoroheptane, perfluorooctane,perfluorodecalin, octafluoropropane, decafluoro-n-butane,perfluorooctylbromide to perfluoroperhydrophenanthrene; and inhalerpropellants like heptafluoropropane and tetrafluoroethane.

With continued reference to FIG. 49, air is dissolved in the urine inthe bladder. As explained above, P_(b) is slightly greater than P_(Air).Here, P_(T)=P_(b)=P_(HD)+P_(Air). In one embodiment, if the material ofthe attenuation device 66 does not allow the higher vapor pressure gasto permeate through the device 66, air is driven into the attenuationdevice until the partial pressure of air in the urine matches thepartial pressure of air in the attenuation device. In anotherembodiment, if a high vapor pressure fluid with a vapor pressure(P_(HD)) greater than the bladder pressure and a low permeability ratethrough the attenuation device wall were put into the attenuation device66, air would be driven into the device 66 until the partial pressuresof air are equal in the attenuation device 66 and in the urine. With areservoir of fluid in the attenuation device 66 more vapor could beevaporated when P_(b) decreases and vapor would condense when the P_(b)increases, thereby resulting in a constant pressure system.

In one embodiment, where the average P_(b) is known, a constant volumesystem is achieved by using a wall material that is generally taut andrigid in structure, such as, for example, silicone, polyurethane or anyderivative thereof, that allows permeability to air but not to theselected high vapor pressure gas or fluid/vapor. Here, the attenuationdevice 66 is placed deflated into the bladder. A mixture of air andhigher vapor pressure gas or fluid are injected into the attenuationdevice 66 so that the P_(HD) matches the average pressure of the bladder(P_(b)) minus the atmospheric pressure (P_(a)). If there is no loss ofthe higher vapor pressure gas or fluid/vapor through the attenuationdevice wall, an equilibrium point is reached when the partial pressureof air in the attenuation device matches the partial pressure of air inurine. If the volume of gas in the attenuation device 66 puts no tensionon the wall of the attenuation device, then the vapor or partialpressure of the higher vapor pressure gas or vapor equals the averagebladder pressure minus the atmospheric pressure and the partial pressureof air in the attenuation device equals the partial pressure of air inthe urine.

It will be noted that the pressure in the bladder typically ranges from0 to 2 psi and is a function of the lifestyle of the individual. In oneembodiment, comprising a constant pressure system, the wall of theattenuation device 66 can be designed to provide tension to controlvolume changes due to pressure variations in the bladder. For example,in one embodiment, if the attenuation device 66 were designed to matchan average bladder pressure of 0.15 psi but the individual's bladderpressure is higher, air would be forced out of the attenuation device 66until the partial pressure of air balances between the attenuationdevice and the urine or all of the air is forced out of the attenuationdevice. If the bladder pressure were lower, air would be driven into theattenuation device until the tension on the walls of the attenuationdevice results in the internal partial pressure of air equaling thebladder partial pressure of air.

Having thus described certain embodiments of the present invention,various alterations, modifications and improvements will be apparent tothose of ordinary skill in the art. Such alterations, variations andimprovements are intended to be within the spirit and scope of thepresent invention. Accordingly, the foregoing description is by way ofexample and is not intended to be limiting. In addition, any dimensionsthat appear in the foregoing description and/or the figures are intendedto be exemplary and should not be construed to be limiting on the scopeof the present invention described herein.

1. A method of treating a patient, comprising the steps of: providing acompressible attenuation device which is moveable from a first,introduction configuration to a second, implanted configuration;introducing the attenuation device into the bladder while in the firstconfiguration; transforming the attenuation device within the bladder tothe second configuration; and attenuating a pressure change within thebladder by reversibly changing the volume of the attenuation device inresponse to the pressure change.
 2. A method as in claim 1, wherein theintroducing step comprises transurethrally introducing the attenuationdevice into the bladder.
 3. A method as in claim 1, wherein theintroducing step comprises placing the attenuation device percutaneouslyinto the bladder.
 4. A method as in claim 1, wherein the transformingstep comprises at least partially inflating the attenuation device.
 5. Amethod as in claim 1, wherein the transforming step comprises permittingthe attenuation device to transform under its own bias.
 6. A method asin claim 1, wherein the transforming step minimizes pressure points inthe bladder.
 7. A method as in claim 1, wherein the attenuating stepcomprises reducing the volume of the attenuation device by at leastabout 5%.
 8. A method as in claim 1, wherein the attenuating stepcomprises reducing the volume of the attenuation device by at leastabout 10%.
 9. A method as in claim 1, wherein the attenuating stepcomprises reducing the volume of the attenuation device by at leastabout 25%.
 10. A method as it, claim 1, wherein the attenuation ofpressure changes within the bladder provides therapeutic benefits alterthe attenuation device is removed.
 11. A method as in claim 1, whereinthe compressible attenuation device is conformable to the shape of thebladder.
 12. A method as in claim 1, wherein the configuration of theattenuation device minimizes pressure points in the bladder.
 13. Amethod of treating a patient, comprising the steps of: providing acompressible attenuation device that is moveable from a first,introduction configuration to a second, implanted configuration;introducing the attenuation device into a treatment site while in thefirst configuration; transforming the attenuation device within thetreatment site to the second configuration; and attenuating a pressurechange within the treatment site by reversibly changing the volume ofthe attenuation device in response to the pressure change.
 14. A methodas in claim 13, wherein the treatment site comprises the bladder.
 15. Amethod as in claim 14, wherein the introducing step comprisestransurethrally introducing the attenuation device into the bladder. 16.A method as in claim 14, wherein the introducing step comprises placingthe attenuation device percutaneously into the bladder.
 17. A method asin claim 13, wherein the treatment site comprises the abdominal cavity.18. A method as in claim 13, wherein the treatment site comprises thebladder wall.
 19. A method as in claim 13, wherein the transforming stepcomprises at least partially inflating the attenuation device.
 20. Amethod as in claim 13, wherein the transforming step comprisespermitting the attenuation device to transform under its own bias.
 21. Amethod as in claim 13, wherein the attenuating step comprises reducingthe volume of the attenuation device by at least about 5%.
 22. A methodas in claim 13, wherein the attenuating step comprises reducing thevolume of the attenuation device by at least about 10%.
 23. A method asin claim 13, wherein the attenuating step comprises reducing the volumeof the attenuation device by at least about 25%.
 24. A method as inclaim 14, wherein the attenuation of pressure changes within the bladderprovides therapeutic benefits after the attenuation device is removed.25. A method as in claim 14, wherein the compressible attenuation deviceis conformable to the shape of the bladder.
 26. A method as in claim 17,wherein the compressible attenuation device is conformable to the shapeof the abdominal cavity.
 27. A method as in claim 18, wherein thecompressible attenuation device is conformable to the shape of thebladder wall.
 28. A method as in claim 13, wherein the introducing stepcomprises introducing the attenuation device into a radicalprostatectomy patient.
 29. A method of implanting a compressibleattenuation device, comprising the steps of: providing the attenuationdevice, the device being moveable from a first, introductionconfiguration to a second, implanted configuration; introducing theattenuation device into a treatment site while in the firstconfiguration; and transforming the attenuation device within thetreatment site to the second configuration.
 30. A method as in claim 29,wherein the treatment site comprises the bladder.
 31. A method as inclaim 30, wherein the introducing step comprises transurethrallyintroducing the attenuation device into the bladder.
 32. A method as inclaim 30, wherein the introducing step comprises placing the attenuationdevice percutaneously into the bladder.
 33. A method as in claim 29,wherein the treatment site comprises the abdominal cavity.
 34. A methodas in claim 29, wherein the treatment site comprises the bladder wall.35. A method as in claim 29, wherein the transforming step comprises atleast partially inflating the attenuation device.
 36. A method as inclaim 29, wherein the transforming step comprises permitting theattenuation device to transform under its own bias.
 37. A method as inclaim 30, wherein the compressible attenuation device is conformable tothe shape of the bladder.
 38. A method as in claim 33, wherein thecompressible attenuation device is conformable to the shape of theabdominal cavity.
 39. A method as in claim 34, wherein the compressibleattenuation device is conformable to the shape of the bladder wail. 40.A method as in claim 29, wherein the introducing step comprisesintroducing the attenuation device into a radical prostatectomy patient.